Natural occurrence and origin of somatically mutated memory B cells in mice.

While most murine peripheral B cells express germline-encoded antibodies of classes M and D (mu+ delta+ cells), small numbers of memory B cells expressing somatically mutated immunoglobulin G antibodies are generated upon T cell-dependent immunization. Analyzing the antibody repertoire of the mu-delta- B cell pool in unimmunized mice, we show that these cells express somatically mutated VH genes and that most of these genes derive from a set of germline VH genes dominantly expressed by mu+delta+ B cells. Thus, class-switched memory B cells are generated in the absence of intentional immunization, presumably in response to environmental antigens. These cells are either recruited from mu+delta+ B cells or selected from newly arising B cells in parallel to the latter, by the same antigens.