DIFFERENTIAL EXPRESSION OF TISSUE-SPECIFIC ADHESION MOLECULES ON HUMAN CIRCULATING ANTIBODY-FORMING-CELLS AFTER SYSTEMIC, ENTERIC, AND NASAL IMMUNIZATIONS - A MOLECULAR-BASIS FOR THE COMPARTMENTALIZATION OF EFFECTOR B-CELL RESPONSES

Expression of the adhesion molecules CD44, L-selectin (CD62L), and int egrin alpha 4 beta 7 by antibody-secreting cells (ASC) was examined in human volunteers after oral, rectal, intranasal, or systemic immuniza tion with cholera toxin B subunit. Almost all blood ASC, irrespective of immunization route, isotype (IgG and IgA), and immunogen, expressed CD44. On the other hand, marked differences were observed between sys temically and intestinally induced ASC with respect to expression of i ntegrin alpha 4 beta 7 and L-selectin, adhesion molecules conferring t issue specificity for mucosal tissues and peripheral lymph nodes, resp ectively. Thus, most ASC induced at systemic sites expressed L-selecti n, whereas only a smaller proportion of ASC expressed alpha 4 beta 7. In contrast, virtually all IgA- and even IgG-ASC detected after perora l and rectal immunizations expressed alpha 4 beta 7, with only a minor fraction of these cells expressing L-selectin. Circulating ASC induce d by intranasal immunization displayed a more promiscuous pattern of a dhesion molecules, with a large majority of ASC coexpressing L-selecti n and alpha 4 beta 7. These results demonstrate that circulating ASC i nduced by mucosal and systemic immunization express different sets of adhesion molecules. Furthermore, these findings provide for the first time evidence for differential expression of adhesion molecules on cir culating ASC originating from different mucosal sites. Collectively, t hese results may explain the anatomical division of mucosal and system ic immune responses in humans as well as the compartmentalization of m ucosal immune responses initiated in the upper vs. the lower aerodiges tive tract.