Role of B cells as antigen-presenting cells in vivo revisited: antigen-specific B cells are essential for T cell expansion in lymph nodes and for systemic T cell responses to low antigen concentrations.
Studies in B cell-deficient mice generated by continuous injection of anti-mu antibodies (muSM) showed that T cell priming in lymph nodes was dependent on antigen presentation by B cells. This concept has recently become controversial since a wide range, from complete deficiency to near normal T cell responses, was reported in studies carried out with B cell-deficient mice generated by gene disruption (muMT). In this study we show that in the absence of B cells, T cell responses are greatly reduced in all the available muMT mouse strains although responses in muMT of the C57BL/6 background (which were used for most studies with muMT) were much more variable and could reach up to 42% of control. In contrast, T cell responses in muMT --> F(1) bone marrow chimeras which have the same phenotype as muMT were totally impaired, suggesting a principle difference between mice developing without B cells (muMT mice) and muSM which are made B cell deficient only after birth. Normal T cell priming was completely restored by reconstitution of muMT and muMT --> F(1) mice with syngeneic B cells. Interestingly, only B cell populations containing antigen-specific B cells were capable of reconstituting T cell responses. Monoclonal B cells taken from Ig transgenic mice could not reconstitute responses to an irrelevant antigen. We also found that B cells were also required for systemic T cell priming when antigen concentrations were limiting but were not required for priming (for T cell help) when mice were immunized with a high antigen dose.
Rivera
A
A
Department of Molecular Genetics and Microbiology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
Chen
C C
CC
Ron
N
N
Dougherty
J P
JP
Ron
Y
Y
D019264:Adoptive Transfer; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation; D001853:Bone Marrow / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D003433:Crosses, Genetic; D004306:Dose-Response Relationship, Immunologic; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D005260:Female; D006433:Hemocyanins / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009113:Muramidase / Q000276:immunology; D011828:Radiation Chimera / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000473:pathology
D000941:Antigens; D018985:Epitopes, B-Lymphocyte; D011947:Receptors, Antigen, B-Cell; D006433:Hemocyanins; C421864:hen egg lysozyme; D009113:Muramidase; C032808:keyhole-limpet hemocyanin