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The Journal of Immunology, 2002, 168: 2173-2181.
Copyright © 2002 by The American Association of Immunologists

Correlation of Tissue Distribution, Developmental Phenotype, and Intestinal Homing Receptor Expression of Antigen-Specific B Cells During the Murine Anti-Rotavirus Immune Response1

Kenneth R. Youngman2,3,*, Manuel A. Franco23{dagger},{ddagger}, Nelly A. Kuklin{dagger},{ddagger}, Lusijah S. Rott*,{dagger},{ddagger}, Eugene C. Butcher2,* and Harry B. Greenberg2,{dagger},{ddagger}

* Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University, and {dagger} Departments of Medicine, Microbiology, and Immunology, Stanford University School of Medicine, Stanford, CA 94305; and {ddagger} Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304

The intestinal homing receptor, {alpha}4{beta}7, helps target lymphocytes to Peyer’s patches (PP) and intestinal lamina propria (ILP). We have previously shown that protective immunity to rotavirus (RV), an intestinal pathogen, resides in memory B cells expressing {alpha}4{beta}7. In this study, using a novel FACS assay, we have directly studied the phenotype of B cells that express surface RV-specific Ig during the in vivo RV immune response. During primary infection, RV-specific B cells first appear as large IgD-B220low{alpha}4{beta}7- and {alpha}4{beta}7+ cells (presumptive extrafollicular, Ab-secreting B cells), and then as large and small IgD-B220high{alpha}4{beta}7- cells (presumptive germinal center B cells). The appearance of B cells with the phenotype of large IgD-B220low{alpha}4{beta}7+ cells in PP and most notably in mesenteric lymph nodes coincides with the emergence of RV-specific Ab-secreting cells (ASC) in the ILP. Thus, these B lymphocytes are good candidates for the migratory population giving rise to the RV-specific ASC in the ILP. RV-specific long-term memory B cells preferentially accumulate in PP and express {alpha}4{beta}7. Nine months after infection most RV-specific IgA ASC are found in PP and ILP and at lower frequency in bone marrow and spleen. This study is the first to follow changes in tissue-specific homing receptor expression during Ag-specific B cell development in response to a natural host, tissue-specific pathogen. These results show that {alpha}4{beta}7 is tightly regulated during the Ag-specific B cell response to RV and is expressed concurrently with the specific migration of memory and effector B cells to intestinal tissues.




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