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The Microenvironment of Human Peyer’s Patches Inhibits the Increase in CD38 Expression Associated with the Germinal Center Reaction

Mark J. Guilliano^*, Amy E. Foxx-Orenstein and Deborah A. Lebman^*

^* Department of Microbiology and Immunology and Department of Medicine, Virginia Commonwealth University, Richmond, VA 23298

Analysis of B cells in the human tonsils identified CD38 expression as a hallmark of germinal center (GC) B cells. However, the signals responsible for the in vivo induction of CD38 have not been determined. The primary site for generation of memory and plasma cells in the gastrointestinal tract is the GCs of Peyer’s patches (PP). PP and intestinal mucosa, but not tonsils or oral mucosa, express mucosal addressin cell adhesion molecule-1 (MAdCAM-1). The ligand for MAdCAM-1, integrin ₄₇, is expressed on naive B cells and memory B cells that traffic to the gastrointestinal tract. In this study we determine that, unlike tonsil, human PP GC B cells do not express significant levels of CD38. PP B cells can be induced to express CD38 upon culture with CD40 ligand, anti-B cell receptor, and IFN-. However, coculture of tonsil naive B cells with an Ab directed against integrin ₇ inhibits IFN--induced CD38 hyperexpression. The absence of CD38 on PP GCs suggests that there are tissue-specific pathways of B cell development that differ between tonsil and PP. The differential expression pattern of MAdCAM-1, together with the observation that ligation of ₇ can inhibit the induction of CD38 expression, suggests that ligation of ₄₇ in vivo may contribute to a PP-specific GC phenotype.