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Function and Regulation of B-cell Subsets in Experimental Autoimmune Arthritis [Elektronisk resurs]

Palm, Anna-Karin E. 1983- (författare)
Kleinau, Sandra (preses)
Cardell, Susanna (opponent)
Uppsala universitet Teknisk-naturvetenskapliga vetenskapsområdet (utgivare)
Uppsala Acta Universitatis Upsaliensis 2015
Engelska 57
Serie: Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology 1651-6214
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  • E-bokAvhandling(Diss. (sammanfattning) Uppsala : Uppsala universitet, 2015)
Sammanfattning Ämnesord
Stäng  
  • B lymphocytes play a significant role in autoimmune arthritis, with their function stretching beyond autoantibody production to cytokine secretion and presentation of autoantigen. However, the involvement and activation of different B-cell subset in the autoimmune response is not fully clear. The main focus of this thesis has been to understand the contribution of marginal zone (MZ) B cells in the induction of collagen-induced arthritis (CIA), a mouse model for rheumatoid arthritis (RA). We show that MZ B cells in the spleen of naïve mice display a natural self-reactivity to collagen type II (CII), the autoantigen used for immunization of CIA. The CII-reactive MZ B cells expand rapidly following immunization with CII, and produce IgM and IgG antibodies to CII. They also very efficiently present CII to cognate T cells in vitro and in vivo . Moreover, absence of regulatory receptors such as CR1/2 or FcγRIIb on the MZ B cells increases their proliferation and cytokine production in response to toll-like receptor, but not B-cell receptor, activation. Further, FcγRIIb-deficient MZ B cells present CII to T cells more efficiently than wild-type MZ B cells. We additionally demonstrate for the first time the existence of a small population of nodal MZ B cells in mouse lymph nodes. Similar to splenic MZ B cells, the nodal MZ B cells expand after CIA induction, secrete IgM anti-CII antibodies and can present CII to cognate T cells. Finally, we show that mast cells, associated with ectopic B cell follicles in inflamed RA joints, in coculture with B cells promote their expansion, production of IgM and IgG antibodies as well as upregulation of CD19 and L-selectin. Coculture with mast cells further causes the B cells to upregulate costimulators and class II MHC, important molecules for antigen-presenting function. In summary, my findings suggest that splenic and nodal self-reactive MZ B cells participate in breaking T-cell tolerance to CII in CIA. B-cell intrinsic regulation is needed to keep such autoreactive B cells quiescent. Mast cells can potentiate B-cell responses locally in the arthritic joint, thus feeding the autoimmune reaction. 

Ämnesord

Natural Sciences  (hsv)
Biological Sciences  (hsv)
Immunology  (hsv)
Naturvetenskap  (hsv)
Biologiska vetenskaper  (hsv)
Immunologi  (hsv)
Biology with specialization in Molecular Immunology  (uu)
Biologi med inriktning mot molekylär immunologi  (uu)

Indexterm och SAB-rubrik

B cells
marginal zone
autoimmune arthritis
spleen
lymph node
antigen presentation
Fc gamma receptor IIb
complement receptors 1 and 2
mast cells
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