IgM+IgD- 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 IgM+IgD+ cells and a minor population (< 5%) of IgM+IgD- cells. In contrast, in gut-associated lymphoid tissue (GALT) derived from individuals undergoing tonsillectomy or appendectomy, IgM+IgD- B cells constitute ~30% of B cells. IgM+IgD- cells isolated from both tonsil and appendix lack plasma cell and B1 cell markers and approximately 50% express the memory marker CD27. Functionally, GALT IgM+IgD- 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 IgM+IgD- 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 IgM+IgD+ cells. Furthermore, clonal lineage analysis reveals that IgM+IgD- clones can include class-switched sequence variants. These findings suggest a maturational scheme starting from CD27-IgM+IgD+ B cells to CD27+IgM+IgD+, and then to CD27-IgM+IgD-, and finally to CD27+IgM+IgD- B cells. In sum, IgM+IgD- 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.