Mucosal memory B cells retain the ability to produce IgM antibodies 2 years after oral immunization.
In recent studies we have demonstrated that immunological B- and T-cell memory may be stimulated effectively by oral immunization, simply by admixing protein antigens with cholera toxin (CT) adjuvant. Here we extend information by employing a hapten-carrier system allowing us to separate B- and T-cell memory and to evaluate the requirement of memory T cells for effective reactivation of mucosal memory B cells. We found that 2 weeks following oral priming immunizations with dinitrophenyl-keyhole limpet haemocyanin (DNP-KLH) plus CT adjuvant, significant serum anti-DNP antibodies of IgG, IgA and IgM immunoglobulin classes were demonstrated. However, after 2 years only IgM anti-DNP antibodies could still be detected in serum. When memory lymphocytes were isolated from these mice, from both systemic and gut-associated lymphoid tissues, and challenged with antigen in vitro, vigorous IgM, but no IgG or IgA, anti-DNP production was observed. By contrast, when the DNP-KHL-primed memory mice were challenged in vivo by an oral booster immunization with DNP-KLH plus CT adjuvant, strong systemic IgG and local mucosal IgA anti-DNP responses were recorded, while IgM anti-DNP production was poor. Moreover, the mucosal memory B cells from DNP-KHL-immunized mice were more responsive in vivo to an oral booster immunization with the carrier-specific antigen, DNP-KLH, compared to that provided by an unrelated carrier, DNP-human serum albumin (HSA), which gave only poor mucosal and systemic anti-DNP B-cell responses. Taken together our data suggest that mucosal memory B cells are recirculating cells that have retained their ability to produce IgM antibodies and, therefore, have not undergone switch differentiation involving gene rearrangements with constant mu-chain deletions. Furthermore, mucosal B-cell memory and CD4+ T-cell memory are closely interconnected phenomena, requiring both components for effective expression and probably also for maintenance of immunological memory in the mucosal immune system.
Vajdy
M
M
Department of Medical Microbiology and Immunology, University of Göteborg, Sweden.
Lycke
N
N
D000284:Administration, Oral; D000818:Animals; D000917:Antibody Formation; D000941:Antigens; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006433:Hemocyanins; D007114:Immunization; D007075:Immunoglobulin M / Q000276:immunology; D007156:Immunologic Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000276:immunology; D013997:Time Factors
C042158:2,4-dinitrophenyl keyhole limpet hemocyanin; D000941:Antigens; D007075:Immunoglobulin M; D006433:Hemocyanins