IgM+IgD− B cells in Human GALT Harbor Characteristics of B1 B cells

Abstract During embryogenesis, B cell lymphopoiesis occurs in fetal liver (FL) and bone marrow (BM). B cells derived from these organs differ in their Ig VH gene usage, their morphological and functional characteristics, and they home to different organs in the mature fetus. Although in mice, FL-B cells are known to home to the peritoneum and GALT, little is known of these cells in humans. We identified a FL-like B cell population representing 10–20% of total B cells in human GALT (appendix and tonsil), but only 1–2% in peripheral blood. These cells express IgM, but not IgD on their surface, spontaneously secrete antibodies in culture, and preferentially class-switch to IgA upon LPS stimulation, three characteristics of FL-B cells. The GALT IgM+IgD− B cells are negative for immature B cell markers CD10 and CD5, plasma cell markers CD38hi and CD138, the activation marker CD43 and the transitional B cell marker CD24hi as expected for FL B cells. In infants and children less than 10 years of age, most (70%) of these IgM+IgD− cells are CD27- non-memory B cells. These data support the hypothesis that the GALT IgM+IgD− B cells are of FL origin. Consistent with this idea, approximately 50% of the B cells in an appendix from a 1-day-old neonate were IgM+IgD−. Deep BCR sequence analysis of these cells will establish their developmental origin.