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VH1–46 Is the Dominant Immunoglobulin Heavy Chain Gene Segment in Rotavirus-Specific Memory B Cells Expressing the Intestinal Homing Receptor ₄₇¹

Jörn-Hendrik Weitkamp^*, Nicole L. Kallewaard, Amber L. Bowen, Bonnie J. LaFleur, Harry B. Greenberg and James E. Crowe, Jr^2,*,

Departments of ^* Pediatrics, Microbiology and Immunology, and Preventive Medicine, Vanderbilt University Medical Center, Nashville, TN 37232; and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305

Memory B cells expressing the intestinal homing marker ₄₇ are important for protective immunity against human rotavirus (RV). It is not known whether the B cell repertoire of intestinal homing B cells differs from B cells of the systemic compartment. In this study, we analyzed the RV-specific V_H and V_L repertoire in human IgD^– B cells expressing the intestinal homing marker ₄₇. The mean frequency of RV-specific B cells in the systemic compartment of healthy adult subjects was 0.6% (range, 0.2–1.2). The mean frequency of IgD^– B cells that were both RV specific and ₄₇ was 0.04% (range, 0.01–0.1), and a mean of 10% (range, 1–32) of RV-specific peripheral blood human B cells exhibited an intestinal homing phenotype. We previously demonstrated that VH1–46 is the dominant Ab H chain gene segment in RV-specific systemic B cells from adults and infants. RV-specific systemic IgD^– or intestinal homing IgD^–/₄₇⁺ B cells in the current study also used the gene segment VH1–46 at a high frequency, while randomly selected B cells with those phenotypes did not. These data show that VH1–46 is the immunodominant gene segment in human RV-specific effector B cells in both the systemic compartment and in intestinal homing lymphocytes. The mean replacement/silent mutation ratio of systemic compartment IgD^– B cells was >2, consistent with a memory phenotype and antigenic selection. Interestingly, RV-specific intestinal homing IgD^–/₄₇⁺ B cells using the VH1–46 gene segment were not mutated, in contrast to systemic RV-specific IgD^– B cells.

This article has been cited by other articles:

				N. L. Kallewaard, B. A. McKinney, Y. Gu, A. Chen, B. V. V. Prasad, and J. E. Crowe Jr. Functional Maturation of the Human Antibody Response to Rotavirus J. Immunol., March 15, 2008; 180(6): 3980 - 3989. [Abstract] [Full Text] [PDF]

				C. Tian, G. K. Luskin, K. M. Dischert, J. N. Higginbotham, B. E. Shepherd, and J. E. Crowe Jr Immunodominance of the VH1-46 Antibody Gene Segment in the Primary Repertoire of Human Rotavirus-Specific B Cells Is Reduced in the Memory Compartment through Somatic Mutation of Nondominant Clones J. Immunol., March 1, 2008; 180(5): 3279 - 3288. [Abstract] [Full Text] [PDF]