Marginal zone B-cell depletion impairs murine host defense against Borrelia burgdorferi infection.
Marginal zone B (MZB) cells are a B-cell subset that produces T-cell-independent antibodies to blood-borne antigens. In this study, we examined the effects of MZB cell depletion on the immune response to the Lyme disease spirochete Borrelia burgdorferi, an extracellular pathogen for which T-cell-independent antibody is an important host defense. MZB cell depletion of C3H/HeJ mice using monoclonal antibody to LFA-1 and alpha(4)beta(1) integrins reduced B. burgdorferi-specific immunoglobulin M (IgM) titers, enhanced pathogen burden, and led to more severe arthritis assessed within the first 2 weeks of infection. In addition, MZB cell-depleted mice had reduced levels of B. burgdorferi-specific IgG, which correlated with diminished splenic CD4+ T-cell-activation, proliferation, and cytokine production. Passive transfer of immune mouse serum from infected control mice into infected MZB cell-depleted mice reduced pathogen burden but did not alter the expression of T-cell activation markers on splenic CD4+ T cells. These findings demonstrate that MZB cells not only are a source of pathogen-specific IgM important for limiting spirochete burden and pathology but also play a prominent role in the priming of splenic T-cell responses to a blood-borne pathogen.
Belperron
Alexia A
AA
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Dailey
Catherine M
CM
Booth
Carmen J
CJ
Bockenstedt
Linda K
LK
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D025065:Borrelia burgdorferi / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018858:Germinal Center; D007113:Immunity, Innate; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D008193:Lyme Disease / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion / Q000379:methods; D051379:Mice; D008809:Mice, Inbred C3H
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007371:Interferon-gamma