IgM+IgD- B Cells in Human Gut-Associated-Lymphoid-Tissue have Memory Features and Give Rise to IgM+ and IgA+ Antibody Secreting Cells. Homo sapiens

IgM+ B cells in humans vary in their level of expression of IgD, with the major circulating population being comprised of IgM+IgD+ cells and a minor population (fewer than 5%) consisting of IgM+IgD- cells. In contrast to the circulation, IgM+ IgD- B cells in gut-associated lymphoid tissue (GALT) derived from individuals undergoing tonsillectomy or appendectomy constitute up to ~30% of B cells. GALT IgM+IgD- cells from both tonsil and appendix lack the plasma cell marker CD138 and are dim for CD38, and approximately 50% of them express the memory marker CD27. Surprisingly, both IgM+IgD-CD27- and IgM+IgD-CD27+ populations show similar antibody repertoires, including overall VH gene usage, level of somatic mutation and clonal diversity. Of note, IgM+IgD- B cells, unlike IgM+IgD+ B cells, exhibit significant clonal overlap with switch memory (IgG+ and IgA+) B cells. Functionally, IgM+IgD- B cells isolated from GALT spontaneously secrete IgM, and class-switch to IgA in response to both T-dependent and T-independent stimulation ex-vivo. Analysis of B cell receptor sequences of tonsil and appendix IgM+IgD- B cells showed that these cells have high levels of somatic hypermutation and high numbers of overlapping clones with memory-switched IgG and IgA B cells, characteristics of antigen-experienced B cells. Taken together, these findings suggest that IgM+IgD- B cells are a memory population that gives rise to switched memory B cells and antibody-secreting cells in the GALT.