Function and regulation of self-reactive marginal zone B cells in autoimmune arthritis

Anna Karin E. Palm, Heike C. Friedrich, Anja Mezger, Maya Salomonsson, Linda Myers, Sandra Kleinau

Research output: Contribution to journalArticle

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Abstract

Polyreactive innate-type B cells account for many B cells expressing self-reactivity in the periphery. Improper regulation of these B cells may be an important factor that underlies autoimmune disease. Here we have explored the influence of self-reactive innate B cells in the development of collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis. We show that splenic marginal zone (MZ), but not B-1 B cells exhibit spontaneous IgM reactivity to autologous collagen II in naïve mice. Upon immunization with heterologous collagen II in complete Freund's adjuvant the collagen-reactive MZ B cells expanded rapidly, while the B-1 B cells showed a modest anti-collagen response. The MZ B cells were easily activated by toll-like receptor (TLR) 4 and 9-ligands in vitro, inducing proliferation and cytokine secretion, implying that dual engagement of the B-cell receptor and TLRs may promote the immune response to self-antigen. Furthermore, collagen-primed MZ B cells showed significant antigen-presenting capacity as reflected by cognate T-cell proliferation in vitro and induction of IgG anti-collagen antibodies in vivo. MZ B cells that were deficient in complement receptors 1 and 2 demonstrated increased proliferation and cytokine production, while Fc receptor IIb deficiency of the cells lead to increased cytokine production and antigen presentation. In conclusion, our data highlight self-reactive MZ B cells as initiators of the autoimmune response in CIA, where complement and Fc receptors are relevant in controlling the self-reactivity in the cells.

Original languageEnglish (US)
Pages (from-to)493-504
Number of pages12
JournalCellular and Molecular Immunology
Volume12
Issue number4
DOIs
StatePublished - Jul 7 2015

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Arthritis
B-Lymphocytes
Collagen
Experimental Arthritis
Fc Receptors
Cytokines
Complement 3d Receptors
Toll-Like Receptor 9
Complement C1
Complement Receptors
Toll-Like Receptor 4
Freund's Adjuvant
Autoantigens
Antigen Presentation
Autoimmunity
Autoimmune Diseases
Immunoglobulin M
Anti-Idiotypic Antibodies
Immunization
Rheumatoid Arthritis

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Function and regulation of self-reactive marginal zone B cells in autoimmune arthritis. / Palm, Anna Karin E.; Friedrich, Heike C.; Mezger, Anja; Salomonsson, Maya; Myers, Linda; Kleinau, Sandra.

In: Cellular and Molecular Immunology, Vol. 12, No. 4, 07.07.2015, p. 493-504.

Research output: Contribution to journalArticle

Palm, Anna Karin E. ; Friedrich, Heike C. ; Mezger, Anja ; Salomonsson, Maya ; Myers, Linda ; Kleinau, Sandra. / Function and regulation of self-reactive marginal zone B cells in autoimmune arthritis. In: Cellular and Molecular Immunology. 2015 ; Vol. 12, No. 4. pp. 493-504.
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