Germinal center B cells lack homing receptors necessary for normal lymphocyte recirculation.

Abstract

Germinal center B cells (GCLC) are a discrete population of antigen-activated lymphoblasts that lack surface IgD and express abundant cell surface binding sites for peanut agglutinin (PNA). These phenotypic features render GCLC easily distinguishable from nearly all plasma cells, T cells and unstimulated B cells and permit identification and isolation of GCLC from antigen-stimulated murine lymphoid organs. The migratory properties of these lymphoblasts were examined in short-term, in vivo homing studies and in an in vitro assay of lymphocyte binding to postcapillary, high endothelial venules (HEV) in frozen sections of Peyer''s patches [PP] and peripheral lymph nodes. In the in vivo experiments, i.v. injected GCLC failed to migrate in significant numbers to peripheral lymphoid organs in comparison with T cells or IgD+ B cells. In the in vitro binding assay, GCLC did not adhere to HEV in either PP or peripheral node sections. A variety of factors, such as preferential sequestration in the liver, may operate in vivo to influence the localization of these cells. Their nearly total failure to migrate into lymphoid organs can best be explained by their inability to recognize and adhere to the specialized HEV, which normally mediate the emigration of recirculating lymphocytes from the blood into these sites. The concept that GCLC fail to express functional homing receptors for HEV was further supported by studies using MEL-14, a monoclonal antibody that appears to recognize the lymphocyte surface receptor for peripheral node HEV; in contrast to most peripheral lymphocytes, GCLC fail to bind MEL-14. These migratory and endothelial-recognition properties of GCLC, when viewed in the context of the possible role of these cells as precursors of plasma cells and/or memory B cells, suggest that the inability of GCLC to recognize HEV may be transient and related to a phase of sessile B cell differentiation.