IgMIgD B cells in human gut-associated lymphoid tissue have memory features and give rise to IgM and IgA antibody-secreting cells.

Human IgM B cells vary in their surface levels of IgD, with the major circulating population of IgMIgD cells and a minor population (< 5%) of IgMIgD cells. In contrast, in gut-associated lymphoid tissue (GALT) derived from individuals undergoing tonsillectomy or appendectomy, IgMIgD B cells constitute ~ 30% of B cells. IgMIgD cells isolated from both tonsil and appendix lack plasma cell and B1 cell markers, and approximately 50% express the memory marker CD27. Functionally, GALT IgMIgD cells spontaneously secrete IgM, and class-switch to IgA in response to both T-dependent and T-independent stimulation ex-vivo. Immune repertoire profiling reveals that GALT IgMIgD cells exhibit lower levels of VH4-34 rearrangements, higher levels of somatic hypermutation, shorter CDR3 sequences and greater clonal overlap with switch memory cells than IgMIgD cells. Furthermore, clonal lineage analysis reveals that IgMIgD clones can include class-switched sequence variants. These findings suggest a maturational scheme starting from CD27IgMIgD B cells to CD27IgMIgD, and then to CD27IgMIgD, and finally to CD27IgMIgD B cells. In sum, IgMIgD B cells in the mucosa have memory features, give rise to class-switched memory B cells and antibody-secreting cells, and likely contribute significantly to the IgA repertoire in human GALT.