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Cover Page

The handle http://hdl.handle.net/1887/44487 holds various files of this Leiden University dissertation

Author: El Bannoudi, Hanane

Title: Immune regulation by CD49b+ CD4+ T cells & modulation of B cell responses

Issue Date: 2016-11-29

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Immune regulation by CD49 Immune regulation by CD49 Immune regulation by CD49

Immune regulation by CD49b b b b

++++

CD4 CD4 CD4 CD4

++++

T cells T cells T cells T cells

& modulation of B cell responses

& modulation of B cell responses & modulation of B cell responses

& modulation of B cell responses

Hanane El Bannoudi

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Immune regulation by CD49b

+

CD4

+

T cells & modulation of B cell responses Hanane El Bannoudi

Painting used for the cover: Aouatif El Ghalbzouri Layout: Hanane El Bannoudi

Printing: Ridderprint BV, the Netherlands Layout cover: Ridderprint BV, the Netherlands

ISBN: 978-94-6299-465-2

©2016 Hanane El Bannoudi

The research leading to the results presented in this thesis has received funding from The European Community’s Seventh Framework Programme FP7, Centre for Medical Systems Biology (CMSB), Dutch Arthritis Foundation, programme Masterswitch, the Netherlands Organisation for Scientific Research (a Vici grant) and the Innovative Medicines Initiative-funded project BeTheCure. Thank you.

Leiden University Medical Center, Leiden University has financially contributed to the

printing of this thesis.

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Immune regulation by CD49b Immune regulation by CD49b Immune regulation by CD49b

Immune regulation by CD49b + ++ + CD4 CD4 CD4 CD4 ++ + + T cells T cells T cells T cells

& modulation of B cell responses

& modulation of B cell responses

& modulation of B cell responses

& modulation of B cell responses

Proefschrift

ter verkrijging van

de graad van Doctor aan de Universiteit Leiden, op gezag van Rector Magnificus prof.mr. C.J.J.M. Stolker,

volgens besluit van het College voor Promoties te verdedigen op dinsdag 29 november 2016

Klokke 16:15 uur

Door

Hanane Hanane Hanane

Hanane E EE El Bannoudi l Bannoudi l Bannoudi l Bannoudi

Geboren te Marokko in 1978

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Promotores Prof.dr. R.E.M. Toes

Prof.dr. T.W.J. Huizinga

Promotiecommissie Prof. dr. F. A. Ossendorp

Prof. dr. C. van Kooten

Prof. dr. P.H.A. Quax

Prof. dr. J. Kuiper

Dr. L. M. van Duivenvoorde (AMC)

Dr. A. Ioan-Fascinay

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Contents

Chapter 1 Introduction 7

Chapter 2 Bridging auto-antibodies and arthritis: the role of Fc receptors 37

Part I Part I Part I

Part I Modulation of B cell responses Modulation of B cell responses Modulation of B cell responses Modulation of B cell responses 57

Chapter 3 Abatacept decreases disease activity in a absence of CD4

+

T cells 59 in a collagen induced arthritis model

Chapter 4 Anti-cyclic citrullinated peptide antibodies are a collection of 79 anti-citrullinated protein antibodies and contain overlapping and

non-overlapping reactivities

Chapter 5 CD28 expressing B cells and ACPA

+

plasmablasts/-cells in 95 Rheumatoid Arthritis patients

Part II Part II Part II

Part II Immune regulation by CD49b Immune regulation by CD49b Immune regulation by CD49b Immune regulation by CD49b

++++

CD4 CD4 CD4 CD4

++++

T cells T cells T cells T cells 109

Chapter 6 DX5

+

CD4

+

T cells modulate CD4

+

T cell response via inhibition of 111 IL-12 production by DCs

Chapter 7 Antigen specificity of CD49b

+

CD4

+

T cells 129

Chapter 8 Summary & discussion 149

Chapter 9 Nederlandse samenvatting 169

Addendum Addendum Addendum

Addendum 177

List of publications 179

Curriculum Vitae 181

Acknowledgment 183

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