Characterization of autoantibody-secreting B cells in mice undergoing stimulatory (chronic) graft-versus-host reactions. Identification of a CD44hi population that binds specifically to hyaluronate

This study was undertaken to identify and isolate the pathophysiologically important B cell subpopulation which is activated to Ig secretion and autoantibody production in stimulatory (chronic) graft-vs-host (GVH) reactions. We recently demonstrated that IL-5 stimulation in vitro induces the appearance of a distinct CD44hi Ialow CD45Rlow B cell subpopulation that has aquired the ability to bind to hyaluronate (HA), one of the ligands for CD44, and that this B cell subpopulation is enriched in both proliferative and Ig-secretory responses. In the present report, CD44 expression was examined in B cells which were activated in the course of stimulatory GVH reactions. Compared with normal mice, B cells from mice undergoing stimulatory GVH reactions contained a novel CD44hi B cell subpopulation which exhibited enhanced binding to HA. The CD44hi HA-adherent B cell subpopulation from GVH mice spontaneously secreted large amounts of Ig, particularly IgG, including autoantibody specific for ssDNA. These findings demonstrate that CD44 expression distinguishes those B cells that are activated in vivo in the course of GVH to proliferate and differentiate into Ig-secreting cells. These CD44hi, HA-adherent, cells may play a prominent role in the hypergammaglobulinemia and immune complex glomerulonephritis that occur during chronic GVH reactions.