(1)Size-dependent effect of IgA on CD89

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(1)Size-dependent effect of IgA on CD89. 6L]HGHSHQGHQW HIIHFW RI ,J$ RQ WKH ,J$ )F 5HFHSWRU &'

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(7) &GRCTVOGPVQH0GRJTQNQI[.GKFGP7PKXGTUKV[/GFKECN%GPVGT.GKFGP6JG0GVJGTNCPFU g&GRCTVOGPVQH+OOWPQNQI[7PKXGTUKV[. *QURKVCN7VTGEJV7VTGEJV6JG0GVJGTNCPFU. 6800$5< 6JG +I# (E TGEGRVQT (Eα4%& KU GZRTGUUGF QP UGXGTCN V[RGU QH EGNNU QH VJG O[GNQKF EGNN NKPGCIG 9G KPXGUVK ICVGFYJGVJGTFKHHGTGPVUK\GUQHJGCVCI ITGICVGF+I# C+I# DKPFVQ%&CPF UWDUGSWGPVN[ KPFWEG EGNNWNCT CEVKXCVKQP #U C OQFGN YG WUGF VJG OWTKPG $ EGNN NKPG ++# VTCPUHGEVGF YKVJ %& QT ++# EGNNU VTCPUHGEVGF YKVJ %& CU YGNNCUYKVJVJG(E4γEJCKPVQUVWF[VJG DKPFKPI QH +I# VQ %& 9JGP VJGUG EGNNU GZRTGUUKPI %& YGTG KPEWDCVGF YKVJ OQPQOGTKE +I# PQ UKIPKHKECPV DKPFKPI QH +I# VQ VJG EGNNU YCU FGVGEV CDNG D[ HNWQTGUEGPEGCEVKXCVGF EGNN UQTVGT CPCN[UKU JQYGXGT KPEWDCVKQP QH VJGEGNNUYKVJCIITGICVGF+I#TGUWNVGFKP v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γEJCKP KU PGEGUUCT[ VQ KP FWEG EGNNWNCT CEVKXCVKQP 1PN[ EGNNU VTCPUHGEVGF YKVJ DQVJ %& CPF VJG (E4 γEJCKP %& γ GPJCPEG VJG +. RTQFWEVKQP VQ HQNF WRQP UVKOWNCVKQPYKVJCIITGICVGUQH+I#(WT VJGTOQTG VTKIIGTKPI QH %& QPN[ TG UWNVU KP KPETGCUG QH KPVTCEGNNWNCT ECNEKWO EQPEGPVTCVKQP =%C ?K KP EGNNU EQGZ RTGUUKPI (E4 γEJCKP /WVCVKQP QH VJG V[TQUKPGTGUKFWGUKPVJG(E4 γEJCKP KO OWPQTGEGRVQT V[TQUKPGDCUGF CEVKXCVKQP OQVKH QH VJG (E4 γEJCKP CDQNKUJGU VJKU KPETGCUG KP =%C ?K KPFKECVKPI CUUQEKC VKQPCPFKPXQNXGOGPVQHVJG(E4γEJCKP KP %& OGFKCVGF UKIPCNKPI. Eur J Immunol 27:2219, 1997. 67.

(8) Chapter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αCPF+N β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γEJCKP YJKEJKUGZRTGUUGFQPO[GNQKFEGNNUKPENQUGCUUQEKCVKQPYKVJ%& KUPQV TGSWKTGFHQTDKPFKPIQHC+I#VQ%&. 0$7(5,$/6$1'0(7+2'6 &HOOFXOWXUH 6JG OWTKPG $ EGNN NKPG ++# YCU VTCPUHGEVGF YKVJ E&0# GPEQFKPI %&. %& QTYKVJE&0#GPEQFKPI%&CUYGNNCUYKVJE&0#GPEQFKPIVJG. 68.

(9) Size-dependent effect of IgA on CD89. OWTKPG(E4γEJCKP %& γ 6JGNCVVGTTGUWNVUKPCRJ[UKECNCUUQEKCVKQPQH %&YKVJVJG(E4γEJCKPCUFGUETKDGFKPFGVCKN #OWVCPVOWTKPG(E4γ EJCKP γ;(;( YCU IGPGTCVGF D[ VYQUVGR QXGTNCR GZVGPUKQP RQN[OGTCUG EJCKP TGCEVKQP 2%4 RTKOGTU HTQO +UQIGP #OUVGTFCO 6JG 0GVJGTNCPFU KP YJKEJ VJG V[TQUKPGU CV RQUKVKQPU CPF YKVJKP VJG +6#/ YGTG EJCPIGF KPVQ RJGP[NCNCPKPGU 6JG KPVGITKV[ QH VJG OWVCPV EQPUVTWEV YCU EQPHKTOGF D[ UGSWGPEG CPCN[UKU ++# EGNNU YGTG EWNVWTGF KP 42/+ OGFKWO UWRRNGOGPVGF YKVJ JGCVKPCEVKXCVGF(%5 42/+(%5 6JG+I#(ETGEGRVQTVTCPUHGEVCPVU%& CPF%& γ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u% CPF GKVJGT WUGF YKVJQWV UK\G UGRCTCVKQP QT HQNNQYKPI UGRCTCVKQP CEEQTFKPIVQUK\GD[UWETQUG FGPUKV[ WNVTCEGPVTKHWICVKQP 6JG NCVVGT YCU RGTHQTOGF KPECNKDTCVGFUWETQUGITCFKGPVUCUFGUETKDGF %LQGLQJRID,J$WR&'H[SUHVVLQJFHOOV #NN DKPFKPI GZRGTKOGPVU YGTG RGTHQTOGF CV u% VQ RTGXGPV GPFQE[VQUKU 2TKQT VQ KPEWDCVKQP++#%& QT%& γ EGNNUYGTGYCUJGFVJTGGVKOGUYKVJEQNF 69.

(10) Chapter 4. 42/+JGCVKPCEVKXCVGF(%5CVu%5WDUGSWGPVN[ZEGNNUYGTGKPEWDCVGF HQT J CV u% KP UKNKEQPK\GF INCUU VWDGU KP zN 42/+ $5# EQPVCKPKPI +C+I# QH FKHHGTGPV UK\G zI KP VTKRNKECVG +P VJG RTGUGPV UVWF[ CRCTV HTQO +OQPQOGTKE O +I# +NCDGNGF CIITGICVGU EQPVCKPKPI HKXG VQ UKZ +I# OQNGEWNGU =C+I#? UGXGP VQ GKIJV +I# OQNGEWNGU =C+I#? CPF GKIJV VQ VGP +I# OQNGEWNGU =C+I#? YGTG WUGF #HVGT KPEWDCVKQP VJG EGNNU YGTG YCUJGF VYKEG YKVJ EQNF 2$5 $5# VQ TGOQXG PQPDQWPF TCFKQCEVKXKV[ CPF VJG COQWPVQHEGNNCUUQEKCVGFTCFKQCEVKXKV[YCUOGCUWTGF#NNFCVCYGTGEQTTGEVGFHQT PQPURGEKHKEDKPFKPIYJKEJYCUNGUUVJCPvQHVJGKPKVKCNKPRWV 'HWHFWLRQRI&' (QT VJG FGVGEVKQP QH %& Z ++# %& QT %& γ EGNNU YGTG YCUJGFVYKEGYKVJ2$5$5#CPFKPEWDCVGFKPVTKRNKECVGHQTJCVu%YKVJ VJG %&URGEKHKE O#D # EWNVWTG UWRGTPCVCPV MKPFN[ RTQXKFGF D[ &T .K 5JGP FKNWVGF KP 2$5 $5# QT CP GSWCN COQWPV QH CP KTTGNGXCPV KUQV[RGOCVEJGF +I) EQPVTQN #D VQ FGVGTOKPG DCEMITQWPF DKPFKPI (QNNQYKPI KPEWDCVKQP EGNNU YGTG YCUJGF VYKEG YKVJ EQNF 2$5 $5# CPF KPEWDCVGF CV u% HQT J YKVJ C 2'NCDGNGF IQCV CPVKOQWUG +I) RQN[ENQPCN CPVKUGTWO. 5QWVJGTP $KQVGEJPQNQI[ $KTOKPIJCO #. FKNWVGF KP 2$5 $5# #HVGT YCUJKPIVYKEGYKVJEQNF2$5$5#EGNNUYGTGHKZGFKPRCTCHQTOCNFGJ[FG KP2$5CPFCPCN[\GFQPC(#%5ECP&CVCCESWKUKVKQPCPFCPCN[UKUYGTGFQPGWUKPI .[UKU++UQHVYCTG $GEVQP&KEMKPUQP5CP,QUG%# %LQGLQJDQGGHWHFWLRQRI,J$ 6Q FGVGEV VJG DKPFKPI QH WPNCDGNGF C+I# VQ %& Z ++# %& QT %& γ EGNNUYGTGYCUJGFVYKEGYKVJ2$5$5#CPFKPEWDCVGFHQTJCV u% YKVJ GKVJGT µION C+I# QT µ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u% #HVGT . 70.

(11) Size-dependent effect of IgA on CD89. OKP µION =C+I#? YCU CFFGF CPF VJG EGNNU YGTG UVCKPGF CPF CPCN[\GF HQT +I#DKPFKPID[(#%5CUFGUETKDGFCDQXG ,/SURGXFWLRQ #HVGTYCUJKPIZ%& QT%& γ EGNNUYGTGKPEWDCVGFYKVJGKVJGT µION O+I# O+I# =C+I#? QT =C+I#? KP 42/+ .25HTGG JGCV KPCEVKXCVGF (%5 KP VTKRNKECVG #HVGT J QH UVKOWNCVKQP UWRGTPCVCPVU YGTG JCTXGUVGF CPF CUUGUUGF HQT +. RTQFWEVKQP KP VJG %6.. RTQNKHGTCVKQP DKQCUUC[ WUKPIVJG+.FGRGPFGPVOWTKPGJ[DTKFQOCEGNNNKPG%6..KPEQODKPCVKQPYKVJ VJG:66EGNNRTQNKHGTCVKQPMKV++ $QGJTKPIGT/CPPJGKO#NOGTG6JG0GVJGTNCPFU QT D[ OGCUWTKPI VJG KPEQTRQTCVKQP QH =*?OGVJKQPKPG z%KYGNN YJKEJ YCU CFFGFHQTVJGNCUVJQWTUQHEWNVWTG%GNNUYGTGJCTXGUVGFWUKPICPCWVQOCVGFEGNN JCTXGUVGT 5MCVTQP .KGT 0QTYC[ 5GTKCN FKNWVKQPU QH OQWUG TGEQODKPCPV +.. 4&U[UVGOU#DKPIFQP7- YGTGWUGFCUCUVCPFCTF &DOFLXPPRELOL]DWLRQDVVD\ 6JG GHHGEV QH ETQUUNKPMKPI %& KP VTCPUHGEVGF ++# $ EGNNU QP ECNEKWO OQDKNK\CVKQP YCU CPCN[\GF WUKPI HNQY E[VQOGVT[ (#%5CP $GEVQP &KEMKPUQP CU FGUETKDGF $TKGHN[ EGNNU YGTG KPEWDCVGF YKVJ µ/ (NWQ CPF µ/ 50#4( /QNGEWNCT 2TQDGU HQT OKP CV u% CHVGT YJKEJ VJG EGNNU YGTG YCUJGFCPFHWTVJGTKPEWDCVGFYKVJCPVK%&O#D/[%GNNUYGTGYCUJGFCPF TWP QP C HNQY E[VQOGVGT HQT U VQ GUVCDNKUJ C DCUGNKPG XCNWG HQT =%C ?K CHVGT YJKEJ ETQUUNKPMKPI IQCV CPVKOQWUG +I/ CPVKDQFKGU YGTG CFFGF %GNNU YKVJQWV RTGXKQWUKPEWDCVKQPYKVJ/[UGTXGFCUPGICVKXGEQPVTQN. 5(68/76 %LQGLQJRID,J$LV&'GHSHQGHQW #U DGHQTG VJG ++# %& CPF %& γ EGNNU YGTG CPCN[\GF HQT %& GZRTGUUKQPD[(#%51PN[EGNNUVTCPUHGEVGFYKVJE&0#EQPVCKPKPI%& %& CPF %& γ YGTG HQWPF RQUKVKXG HQT %& 0Q GZRTGUUKQP QH %& YCU FGVGEVGF QP VJG ++# EGNN NKPG (KIWTG 6Q CUUGUU YJGVJGT CIITGICVGF +I# DKPFUVQ%&VJGEGNNNKPGU++#%& CPF%& γ EGNNUYGTGKPEWDCVGF YKVJµIONWPNCDGNGFJGCVCIITGICVGFUGTWO+I# C+I# CPFCPCN[\GFHQT+I# DKPFKPID[(#%57PNCDGNGFC+I#YCUCDNGVQDKPFQPN[VQ%&GZRTGUUKPIEGNN NKPGUTGUWNVKPIKPv+I#RQUKVKXGEGNNU0QUKIPKHKECPVDKPFKPIQHC+I#VQ VJG++#EGNNU YCU FGVGEVGF (KIWTG 6JKU KPFKECVGF VJCV VJG DKPFKPI QH C+I# YCU%&FGRGPFGPV. 71.

(12) Chapter 4. CD89+. Relative cell number. IIA1.6. CD89+/γ+. CD89. 100. 101. 102. 103. 104100. 101. 102. 103. 104 100. 101. 102. 103. 104. 103. 104100. 101. 102. 103. 104 100. 101. 102. 103. 104. aIgA. 100. 101. 102. Figure 1. CD89 expression levels on IIA1.6, CD89+ and CD89+/γ+ cells (upper panel). CD89 expression was detected by FACS, as described above. Lower panel: staining of surface-bound aIgA on and IIA1.6, CD89+ + + cells. Cells CD89 /γ were stained for surfacebound IgA after incubation for 1 h at 4°C in the presence of 20 µg/ml unfractionated aIgA.. Log fluoresence intesity. A CD89+. Relative cell number. IIA1.6. CD89+/γ+. mIgA1. 100. 101. 102. 103 104 100 101. 102. 103. 104 100 101. 102. 103. 104. 103 104 100 101. 102. 103. 104 100 101. 102. 103. 104. aIgA1. 100. 101. 102. Log fluoresence intesity. B CD89+. Relative cell number. IIA1.6. CD89+/γ+. mIgA2. 100. 101. 102. 103 104 100 101. 102. 103. 104 100 101. 102. 103. 104. 103 104 100 101. 102. 103. 104 100 101. 102. 103. 104. aIgA2. 100. 101. 102. Log fluoresence intesity. 72. Figure 2. (A) Staining of surface-bound IgA to and IIA1.6, CD89+ + + CD89 /γ cells as detected by FACS. Cells were stained for surfacebound IgA after incubation for 1 h at 4°C in the presence of 20 µg/ml mIgA1 (upper panel) or [aIgA1]5-6. (B) Staining was done as described for (A); however, IgA2 instead of IgA1, was used..

(13) Size-dependent effect of IgA on CD89. 6L]HGHSHQGHQWELQGLQJRID,J$WR&'EHDULQJFHOOV 6QCUUGUUYJGVJGTDKPFKPIQHVJGC+I#KUFGRGPFGPVQPVJGUK\GQHVJGCIITGICVGUQH +I# O+I# CPF O+I# YGTG NCDGNGF YKVJ + JGCVCIITGICVGF CPF HTCEVKQPCVGF D[ UK\G WUKPI UWETQUGFGPUKV[ WNVTCEGPVTKHWICVKQP 6JG EGNN NKPGU ++# %& QT. %& γ YGTG KPEWDCVGF YKVJ µION + NCDGNGF O+I# =C+I#? =C+I#? =C+I#? O+I# =C+I#? =C+I#? =C+I#? CPF CUUGUUGF HQTDKPFKPI++#EGNNUQPN[UJQYGF DCEMITQWPF DKPFKPIQH CNN +I# RTGRCTCVKQPU. (KIWTG 8GT[NKVVNGDKPFKPIQHDQVJO+I#CPFO+I#VQVJG%&GZRTGUUKPI EGNN NKPGU YCU QDUGTXGF *QYGXGT =C+I#? CPF =C+I#? YGTG CDNG VQ DKPF VQ. aIgA bound (cpm). 2500. 125. VJG %&GZRTGUUKPI EGNNU GHHKEKGPVN[ (WTVJGT CIITG ICVKQP QH C+I# TGUWNVGF KP FKOKPKUJGF DKPFKPI QH VJG CIITGICVGU VQ DQVJ %& CPF %& γ EGNNU CU EQORCTGF VQ =C+I#?. (KIWTG . IIA1.6. 2000 1500 1000 500 0 mIgA. 1. aIgA1. 5-6. aIgA1. 7-9. aIgA1. 9-11. mIgA. 2. aIgA2. 5-6. aIgA bound (cpm) 125. 9-11. 1500 1000 500. mIgA. 1. aIgA1. 5-6. aIgA1. 7-9. aIgA1. 9-11. mIgA. 2. aIgA2. 5-6. aIgA2. 7-9. aIgA2. 9-11. CD89+/γ+. 4000. aIgA bound (cpm). aIgA2. 2000. 0. 125. 7-9. CD89+. 2500. Figure 3. Binding of different sizes of 125I-aIgA to IIA1.6 (upper panel), CD89+ (middle panel) and (lower panel) CD89+/γγ+cells. Cells (1x106) were incubated in triplicate for 16 h at 4°C in the presence of 20 µg/ml 125I-labeled mIgA1, [aIgA1]5-6, [aIgA1]7-9, [aIgA1]9-11, mIgA2, [aIgA2]5-6, [aIgA2]7-9 or [aIgA1/2]9-11. After incubation, cells were washed and the radioactivity bound to the cells was measured. Results are expressed as the mean ± SEM.. aIgA2. 3000. 2000. 1000. 0 mIgA. 1. aIgA1. 5-6. aIgA1. 7-9. aIgA1. 9-11. mIgA. 2. aIgA2. 5-6. aIgA2. 7-9. aIgA2. 9-11. 7KHELQGLQJRID,J$LV&'VSHFLILF 6Q FGHKPG VJG URGEKHKEKV[ QH VJG DKPFKPI QH C+I# VQ VJG %& GZRTGUUKPI EGNNU WPNCDGNGF=C+I#?YCUKPEWDCVGFYKVJ%& γ EGNNUKPVJGRTGUGPEGQTCDUGPEG QHVJGCPVK%&O#D/[6JGDKPFKPIQH=C+I#?VQVJG%& γ EGNNUYCU KPJKDKVGF D[ VJG CPVK%& O#D /[ D[ CNOQUV KPFKECVKPI VJCV VJG DKPFKPIQH=C+I#?VQVJGEGNNUYCU%&URGEKHKE (KIWTG 73.

(14) Chapter 4. 7KH)F5JDPPDFKDLQLVQHFHVVDU\IRUDFWLYDWLRQYLD&' 6Q FGVGTOKPG YJGVJGT C+I# KU CDNG VQ KPFWEG CEVKXCVKQP QH VJG EGNN XKC %& %& CPF %& γ EGNNU YGTG KPEWDCVGF YKVJ µION WPNCDGNGF O+I# =C+I#? O+I# =C+I#? QT OGFKWO CNQPG HQT JQWTU CV u% #HVGT KPEWDCVKQP UWRGTPCVCPVU YGTG JCTXGUVGF CPF CUUGUUGF HQT +. RTQFWEVKQP $QVJ =C+I#?CPF=C+I#?YGTGCDNGVQKPETGCUGVJG+.RTQFWEVKQPQH%& γ. Relative cell number. EGNNUVQHQNFCUEQORCTGFVQEGNNUKPEWDCVGFKPOGFKWOCNQPGO+I#CPF O+I# HCKNGF VQ KPFWEG C UKIPKHKECPV +. RTQFWEVKQP QH VJG %& γ EGNNU 0Q UKIPKHKECPV +. RTQFWEVKQP YCU QDUGTXGF CHVGTKPEWDCVKQPQH%& EGNNUYKVJO+I# O+I#=C+I#?QT=C+I#?HQTJCV u% KPFKECVKPI VJCV HQT VTKIIGTKPI QH VJG EGNNU XKC %& GZRTGUUKQP QH (E4 γEJCKP KU PGEGUUCT[. 100. 101. 102. 103. 104. Log fluoresence intesity. Figure 4. Specificity of the binding of [aIgA]5-6 to CD89. CD89+/γ+ cells were incubated at 4°C for 30 min with 20 µg/ml [aIgA]5-6 in the presence (filled histogram) or absence (open histogram) of antiCD89 mAb My43 culture supernatant diluted 1/5 in PBS/0.5% BSA and analyzed for IgA binding by FACS as described above. Background staining of the cells is shown by the stippled histogram.. 0XWDWLRQ RI WKH W\URVLQHV ZLWKLQ WKH ,7$0 RI )F5 JDPPDFKDLQ DEROLVKHV>&D@LUHVSRQVHVDIWHU&'FURVVOLQNLQJ. Fluo-3/Snarf-1 Ratio(x1000). 6Q CPCN[\G VJG CUUQEKCVKQP QH VJG (E4 γEJCKP YKVJ %& CPF KVU KPXQNXGOGPV KP UKIPCNVTCPUFWEVKQPCHVGT%&ETQUUNKPMKPIYGOGCUWTGFVJG=%C ?KCHVGTETQUU NKPMKPIQH%&KP%& %& γ CPF%& γ;(;( EGNNU. 2 CD89+/γ+ CD89+/γY65F-76F+. 1. CD89+ 0 0. 48. 96. 144. time (sec). 74. 192. 240. Figure 5. Calcium mobili-zation. Calcium mobilization was triggered in Fluo-3/ SNARF-1 loaded IIA 1.6 B cells transfected with CD89+ (--),CD89+/γ+ or CD89+/ γY65F-Y76F+ (…….). Cells were incubated with antiCD89 mAb My43 for 30 min at room temperature after which CD89 was cross-linked with goat anti-mouse IgM Ab (arrow). [Ca2+]i was measured using flow cytometry as described above. Data shown are representative of four separate experiments with similar results..

(15) Size-dependent effect of IgA on CD89. %TQUUNKPMKPIQH%&QP%& γ EGNNUTGUWNVGFKPCUVTQPIKPETGCUGKP=%C ?+ TGCEJKPICOCZKOWOCHVGTvUYJKNGETQUUNKPMKPIQH%&KP%& EGNNUJCF PQGHHGEVQP=%C ?K/WVCVKQPQHVJGV[TQUKPGUYKVJKPVJG+6#/QHVJG(E4γEJCKP KP VJG %& γ;(;( EGNNU CDQNKUJGF VJKU KPETGCUG KP =%C ?K CHVGT ETQUU NKPMKPIQH%& (KIWTG . ',6&866,21 +P +I# PGRJTQRCVJ[ VJG OQUV EQOOQP V[RG QHINQOGTWNQPGRJTKVKU FGRQUKVKQP QH +I#KPVJGTGPCNOGUCPIKWOKUQDUGTXGF6JGUG+I#EQORNGZGUVQIGVJGTYKVJ+I) CPFEQORNGOGPVEQORQPGPVUUWEJCU%CTGVJQWIJVVQDGETWEKCNHQTVJGQPUGV QHVJGKPHNCOOCVQT[RTQEGUUKP+I#PGRJTQRCVJ[5GXGTCNTGRQTVUJCXGUJQYPVJCV FKOGTKE CPF RQN[OGTKE DWV PQV OQPQOGTKE HQTOU QH +I# CTG OQTG GHHKEKGPV KP GPJCPEKPI VJG RTQFWEVKQP QH KPHNCOOCVQT[ E[VQMKPGU UWEJ CU 60(α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α CPF%αFQOCKPUQHVJG+I#OQNGEWNGVQCNNQYGHHKEKGPVDKPFKPIVQ%& /QPQOGTKE +I# UGGOU VQ JCXG NKVVNG CHHKPKV[ HQT %& CU EQORCTGF VQ NCTIGT EQORNGZGUQHC+I#6JKUKUKPCITGGOGPVYKVJVJGHKPFKPIVJCVQPN[RQN[OGTKEHQTOU QH+I#DKPFGHHKEKGPVN[VQGIOGUCPIKCNEGNNU 0QFKHHGTGPEGYCUQDUGTXGF KPVJGDKPFKPIQH+I#QT+I# 6JG (E4 γ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

(16) Chapter 4. +.RTQFWEVKQPKU(E4γEJCKPFGRGPFGPVUKPEGQPN[VJG%& γ EGNNUGZRTGUUKPI VJG (E4 γEJCKP CTG CDNG VQ KPFWEG UKIPCN VTCPUFWEVKQP WRQP UVKOWNCVKQP YKVJ. RQN[OGTKE +I# +PCFFKVKQPVJGKPETGCUGKP=%C ?KCHVGTETQUUNKPMKPIQH %&KUQPN[RTGUGPVKPEGNNUGZRTGUUKPIVJG(E4γEJCKP9JGPVJGV[TQUKPGUYKVJKP VJG +6#/ CTG OWVCVGF KPVQ RJGP[NCNCPKPGU PQ KPETGCUG KP =%C ?K KU HQWPF KPFKECVKPI VJCV CP KPVCEV +6#/ KU PGEGUUCT[ HQT HWPEVKQPCN CEVKXKV[ 6JKU GZRGTKOGPV ENGCTN[ UJQYU VJCV VJG (E4 γEJCKP KU CUUQEKCVGF YKVJ %& CPF KU KPXQNXGF KP UKIPCNKPI CHVGT ETQUUNKPMKPI QH %& (WTVJGTOQTG QWT TGUWNVU FGOQPUVTCVG VJCV HQT DKPFKPI QH C+I# VQ %& VJG (E4 γEJCKP KU PQV GUUGPVKCN. DGECWUGDQVJ%& CUYGNNCU%& γ EGNNUDKPFC+I#GHHKEKGPVN[ 6JGUGFCVCUJQY VJCV %& KPVGTCEVU RTGHGTGPVKCNN[ YKVJ UOCNN +I#EQPVCKPKPI CIITGICVGUQHHKXGVQUKZ+I#OQNGEWNGURGTCIITGICVGYJGTGCUOQPQOGTKE+I#QT NCTIG+I#EQPVCKPKPICIITGICVGUDKPFVQ%&VQCNGUUGTGZVGPV(WTVJGTOQTGVJG (E4γEJCKPCNVJQWIJGUUGPVKCNHQTCEVKXCVKQPKUPQVTGSWKTGFHQTDKPFKPIQH+I#VQ %&. 76.

(17) Size-dependent effect of IgA on CD89. 5()(5(1&(6 *GTGOCPU ,( CPF KP 5GNC / 6JG #PVKIGPU+P6JG#PVKIGPU*GTGOCPU,(CPFKP 5GNC / GFU #ECFGOKE 2TGUU 0GY ;QTM R /GUVGEM[,CPF,4/E)JGG+O OWPQINQDWNKP # +I# OQNGEWNCT CPF EGNNWNCT KPVGTCEVKQPU KPXQNXGF KP +I# DKQU[PVJGUKU CPF KOOWPG TGURQPUG #FX +OOWPQN 4KEJCTFU%&CPF,)CWNFKG+I# OGFKCVGF RJCIQE[VQUKU D[ OQWUG CNXGQNCT OCETQRJCIGU#O4GX4GURKT&KU )QTVGT # 2 5 *KGOUVTC 0 -NCT /QJCOCF . # XCP 'U CPF / 4 &CJC $KPFKPI KPVGTPCNK\CVKQP CPF FGITCFCVKQP QHUQNWDNGCIITGICVGUQHJWOCPUGETGVQT[+I#D[ TGUKFGPV TCV RGTKVQPGCN OCETQRJCIGU +OOWPQN QI[ /CNKU\GYUMK % 4 . 5JGP CPF / 9 (CPIGT 6JG GZRTGUUKQP QH TGEGRVQTU HQT +I#QPJWOCP OQPQE[VGU CPF ECNEKVTKQNVTGCVGF *.EGNNU,+OOWPQN .QYGNN)*.(5OKVJ/5#TVGPUVGKP ) 5 0CUJ CPF 4 2 , /CE&GTOQVV #PVKDQF[FGRGPFGPV EGNNOGFKCVGF CPVKDCEVGTKCN CEVKXKV[ QH JWOCP OQPQPWENGCT EGNNU + - N[O RJQE[VGU CPF OQPQE[VGU CTG GHHGEVKXG CICKPUV OGPKPIQEQEK KP EQQRGTCVKQP YKVJ JWOCP KOWPG UGTC,'ZR/GF .QYGNN ) * . ( 5OKVJ , / )TKHHKUU CPF $ . $TCPFV +I#FGRGPFGPV OQPQE[VGOGFKCVGFCPVKDCEVGTKCNCEVKXKV[,'ZR /GF /CE+PV[TG ' # 2 , 4QDGTVU / ,QPGU % ' XCP FGT 5EJQQV ' , (CXCNCTQ 0 6KFOCPCPF&%.KPEJ#EVKXCVKQPQH JWOCP OQPQE[VGU QEEWTU QP ETQUUNKPMKPI OQPQE[VKE CPVKIGPU VQ CP (E TGEGRVQT , +OOW PQN 5JGP.#OQPQENQPCNCPVKDQF[URG EKHKE HQT KOOWPQINQDWNKP # TGEGRVQT VTKIIGTU RQN[OQTRJQPWENGCT PGWVTQRJKN UWRGTQZKFG TG NGCUG,.GWMQE$KQN. 2QNCV).,.CWHGT+(CDKCPCPF,* 2CUUYGNN %TQUUNKPMKPI QH OQPQE[VG RNCUOCOGODTCPG(ECNRJC(EICOOCQTOCP PQUGTGEGRVQTU KPFWEGU 60( RTQFWEVKQP +OOW PQNQI[ 2CVT[ % # *GTDGNKP # .GJWGP , ( $CEJ CPF 4 % /QPVGKTQ (E CNRJC TG EGRVQTUOGFKCVGTGNGCUGQHVWOQWTPGETQUKUHCE VQT CNRJC CPF KPVGTNGWMKP D[ JWOCP OQPQ E[VGU HQNNQYKPI TGEGRVQT CIITGICVKQP +OOWPQN QI[ 4GVGTKPM 6 , ' 9 .GXCTJV 0 -NCT /QJCOCF . # XCP 'U CPF / 4 &CJC 6TCPUHQTOKPI ITQYVJ HCEVQTDGVC . 6)(DGVC FQYPTGIWNCVGU +I# (E TGEGRVQT. %& GZRTGUUKQP QP JWOCP OQPQE[VGU %NKP 'ZR+OOWPQN 5JGP . 4% /QPVGKTQ &CJC /4 * -WDCICYC CPF /& %QQRGT %& ENWUVGTYQTMUJQRTGRQTV+P.GWMQE[VGV[RKPI8 5EJNQUUOCP GV CN GF 1ZHQTF 7PKXGTUKV[ 2TGUU 1ZHQTFR /CNKU\GYUMK % 4 % , /CTEJ / # 5EJQGPDQTP 5 )KORGN CPF . 5JGP 'ZRTGUUKQP ENQPKPI QH C JWOCP (E TGEGRVQT HQT +I#,'ZR/GF /QPVGKTQ 4 % / & %QQRGT CPF * -WDCICYC /QNGEWNCT JGVGTQIGPGKV[ QH (ECNRJCTGEGRVQTUFGVGEVGFD[TGEGRVQTURGEKHKE OQPQENQPCNCPVKDQFKGU,+OOWPQN 5JGP . 4GEGRVQTU HQT +I# QP RJCIQE[VKEEGNNU+OOWPQN4GU )QOG\)WGTTGTQ % ' )QP\CNG\ CPF , 'IKFQ'XKFGPEGHQTCURGEKHKE+I#TGEGR VQTKPTCVCPFJWOCPOGUCPIKCNEGNNU,+OOWPQN /QPVGKTQ4%*-WDCICYCCPF/& %QQRGT%GNNWNCTFKUVTKDWVKQPTGIWNCVKQP CPFDKQEJGOKECNPCVWTGQHCP(ECNRJCTGEGRVQT KPJWOCPU,'ZR/GF .WO.)#8/WEJOQTG&-GTGP, &GEMGT+-QUMK95VTQDGTCPF4/$NCGUG # TGEGRVQT HQT +I# QP JWOCP 6 N[O RJQE[VGU,+OOWPQN 77.

(18) Chapter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

(19) Size-dependent effect of IgA on CD89 5JGP . 4 .CUUGT CPF / 9 (CPIGT /[ C OQPQENQPCN CPVKDQF[ VJCV TG CEVUYKVJJWOCPO[GNQKFEGNNUKPJKDKVUOQPQE[VG +I# DKPFKPI CPF VTKIIGTU HWPEVKQP , +OOWPQN 8CP FGP *GTKM1WFKLM + ' 0 # 9GUVGTFCCN 0 8 *GPTKSWG\ 2 , %CRGN CPF ,)XCPFG9KPMGN(WPEVKQPCNCPCN[UKU QH JWOCP (E ICOOC 4++ %& KUQHQTOU GZ RTGUUGFKP$N[ORJQE[VGU,+OOWPQN )QOG\)WGTTGTQ%/,.QRG\#TOCFC ' )QP\CNG\ CPF , 'IKFQ 5QNWDNG +I# CPF +I) CIITGICVGU CTG ECVCDQNK\GF D[ EWNVWTGF TCV OGUCPIKCN EGNNU CPF KPFWEG RTQFWEVKQP QH 60(CNRJCCPF+.CPFRTQNKHGTCVKQP,+OOW PQN 5W\WMK;66UWIG;6QOKPQ-5CKVQ CPF 4 # %JKUGK 2QUUKDNG EQPVTKDWVKQP QHVJG(ECNRJC4GEGRVQTQPVJG/GUCPIKCNEGNNU VQVJGRCVJQIGPGUKUQH+I#0GRJTQRCVJ[,#O 5QE0GRJTQN 5 #DUVTCEV. %CTC[CPPQRQWNQU . , / *GZJCO CPF , & %CRTC .QECNK\CVKQP QH VJG DKPFKPI UKVGHQTVJGOQPQE[VGKOOWPQINQDWNKP +I #(E TGEGRVQT %& VQ VJG FQOCKP DQWPFCT[ DG VYGGP %CNRJC CPF %CNRJC KP JWOCP +I# , 'ZR/GF -GGICP#&CPF9'2CWN/WN VKEJCKP KOOWPG TGEQIPKVKQP TGEGRVQTU UKOKNCTK VKGU KP UVTWEVWTG CPF UKIPCNKPI RCVJYC[U +OOW PQN6QFC[ %CODKGT , % #PVKIGP CPF (E TG EGRVQT UKIPCNKPI 6JG CYGUQOG RQYGT QH VJG KOOWPQTGEGRVQTV[TQUKPGDCUGFCEVKXCVKQPOQVKH. +6#/ ,+OOWPQN /QTVQP*%/XCP'IOQPFCPF,) ,XCPFG9KPMGN5VTWEVWTGCPFHWPEVKQP QHJWOCP+I#(ETGEGRVQTU (ECNRJC4 %TKV 4GX+OOWPQN. 79.

(20) Chapter 4. 80.

(21)

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