Analysis of somatic mutation and class switching in naive and memory B cells generating adoptive primary and secondary responses.
Clonal progeny of naive B cells (producing a primary antibody response) and of memory B cells (producing a secondary response) were identified in a cell transfer system. Primary response clones are typically derived from IgM precursors and express unmutated V regions. Multiple isotype switches occur in these clones. Secondary response clones derive from IgG1 precursors and express highly mutated V regions. Additional switches do not occur. With one exception, there was no evidence for somatic mutation during clonal expansion. The generation of mutated memory cells may thus represent a distinct differentiation pathway. Evidence is presented that, in this pathway, mutants that have lost antigen binding specificity but that remain available for stimulation by a different antigen arise upon antigenic stimulation.
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D002478:Cells, Cultured; D002999:Clone Cells; D005796:Genes; D007116:Immunization, Passive; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007156:Immunologic Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics
D007135:Immunoglobulin Variable Region; D012333:RNA, Messenger