Mucosally activated circulating human B cells in diarrhea express homing receptors directing them back to the gut

Background & Aims: Recirculation of mucosal lymphocytes has been established in animals but not in humans. Specific antibody-secreting cells in the blood of patients with diarrhea, initially activated in gut mucosa, are potential recirculating cells. The aim of this study was to determine whether these cells circulate back to gut by analyzing their homing receptors. Methods: Blood mononuclear cells, separated with immunomagnetic cell sorting into receptor-positive and receptor-negative populations, were assayed for pathogen-specific antibody-secreting cells and all immunoglobulin-secreting cells using enzyme-linked immunospot assay. Results: The gut mucosa homing receptor alpha(4) beta(7) was expressed more frequently on pathogen-specific antibody-secreting cells than on immunoglobulin-secreting cells of healthy controls (P < 0.001). Conversely, L-selectin, a homing receptor for peripheral lymph nodes, was found on remarkably fewer antibody-secreting cells of the patients compared with immunoglobulin-secreting cells of controls (32.9% and 70.3%, respectively; P < 0.001). Three to 6 months after the disease, specific antibody-secreting cells had disappeared and frequency of L-selectin-and alpha(4) beta(7)-expressing cells had returned to control levels. Conclusions: Circulating mucosally activated antibody-secreting cells express a set of homing receptors guiding them back to the gut. This provides evidence for recirculation of mucosal lymphocytes in humans.