CD21 CD23 follicular B cells express antigen-specific secretory IgM mRNA as primary and memory responses.

CD21 CD23 IgM mouse follicular B cells comprise the bulk of the mature B-cell compartment, but it is not known whether these cells contribute to the humoral antibody response. We show using a direct RT-PCR method for antigen-specific VH, that FACS-sorted mouse CD21 CD23 B cells express specific secretory IgM VH transcripts in response to immunization and also exhibit a memory response. The secretory IgM expressed is distinct from the IgG expressed by cells of this phenotype, which we also analyse here, having a distinct broader distribution of CDR-H3 sequences and zero or low levels of somatic mutation in the region analysed. These results imply that cells of the CD21 CD23 phenotype have distinct IgM and IgG populations that contribute directly to the humoral antibody and memory responses by expressing antigen-specific secretory immunoglobulin. We also argue that the more diverse CDR-H3 sequences expressed by antigen-experienced IgM CD21 CD23 follicular B cells would place them at the bottom of a recently hypothesized memory B-cell hierarchy.