Nodal marginal zone B cells in mice: a novel subset with dormant self-reactivity.
Marginal zone (MZ) B cells, representing a distinct subset of innate-like B cells, mount rapid T-independent responses to blood-borne antigens. They express low-affinity polyreactive antigen receptors that recognize both foreign and self-structures. The spleen is considered the exclusive site for murine MZ B cells. However, we have here identified B cells with a MZ B-cell phenotype in the subcapsular sinuses of mouse lymph nodes. The nodal MZ (nMZ) B cells display high levels of IgM, costimulators and TLRs, and are represented by naïve and memory cells. The frequency of nMZ B cells is about 1-6% of nodal B cells depending on mouse strain, with higher numbers in older mice and a trend of increased numbers in females. There is a significant expansion of nMZ B cells following immunization with an autoantigen, but not after likewise immunization with a control protein or with the adjuvant alone. The nMZ B cells secrete autoantibodies upon activation and can efficiently present autoantigen to cognate T cells in vitro, inducing T-cell proliferation. The existence of self-reactive MZ B cells in lymph nodes may be a source of autoantigen-presenting cells that in an unfortunate environment may activate T cells leading to autoimmunity.
Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
Anna-Karin E
AK
Palm
Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
Heike C
HC
Friedrich
Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
Sandra
S
Kleinau
D000818:Animals; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D049109:Cell Proliferation; D005260:Female; D007075:Immunoglobulin M / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology* / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D013154:Spleen / Q000166:cytology / Q000276:immunology
D001324:Autoantigens; D007075:Immunoglobulin M