B-1 B cell IgM antibody initiates T cell elicitation of contact sensitivity.
Although B-1 B cells have received considerable attention, their actual role in the normal functioning of the immune system is unclear. The hypothesized role of B-1 cell IgM in natural protective immunity is just being established. We have uncovered a separate and novel role for B-1 cell IgM in initiating the elicitation of acquired T cell-dependent contact sensitivity (CS), the prototype of in vivo T cell immunity, early after immunization (within 4 days). The recent recognition of a similarly unanticipated role of B cells in a variety of T cell responses, may indicate that B-1 cell IgM has a broader role in immunity than thought previously. We showed that 24 hr CS responses, and rises in local IFN-gamma levels at 24 hrs later after antigen (Ag) challenge the ears, were absent in pan B cell and antibody deficient mice. The mechanism of B cell involvement in CS-initiation is via local C5a generation early (1-2 hrs) after antigen (Ag) challenge of the ears, in 4 day contact sensitized mice. C5a activates local mast cells to release serotonin (5-HT) and TNF alpha to induce endothelial ICAM-1 and VCAM-1, leading to T cell recruitment. We hypothesized that C5a was generated via complement activation due to antibodies forming local AgAb complexes, and that B-1 cell IgM was involved because isotype switching of B-2 cells to produce C-activating IgG isotypes, could not occur as early as day 4. Indeed, B-1 cell deficient CBA/N-xid mice lacked C5a in 2 hr ear extracts, and had impaired CS ear swelling and elaboration of IFN-gamma at 24 hrs. Importantly, adoptive transfer of purified normal peritoneal B-1 cells, or just i.v. injection of Ag-specific IgM monoclonal antibodies in sensitized xid, restored deficient early C5a and late 24 hr ear swelling. These results suggest that early after Ag challenge, specific B-1 cell IgM, produced at distant sites by prior sensitization, forms AgAb complexes that trigger elaboration of C5a, to activate mast cell release of vasoactive TNF alpha and 5-HT to initiate CS, leading to T cell recruitment. We postulate that antibody of various isotypes possibly may lead to local vascular activation to aid in T cell recruitment in a variety of T cell responses, but that very early after immunization, Ag-specific IgM produced by B-1 cells, preferentially serves this important function.
Askenase
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PW
Section of Allergy and Clinical Immunology, Dept. of Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Tsuji
R F
RF
D019264:Adoptive Transfer; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000637:transplantation; D003167:Complement Activation; D015936:Complement C5a / Q000172:deficiency / Q000276:immunology; D003877:Dermatitis, Contact / Q000276:immunology*; D004423:Ear; D006801:Humans; D007113:Immunity, Innate; D007114:Immunization; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology*; D007153:Immunologic Deficiency Syndromes / Q000276:immunology; D007371:Interferon-gamma / Q000097:blood; D008213:Lymphocyte Activation / Q000276:immunology*; D008407:Mast Cells / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D012701:Serotonin / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D014409:Tumor Necrosis Factor-alpha; D012701:Serotonin; D015936:Complement C5a; D007371:Interferon-gamma