The Journal of Experimental Medicine
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Published 1 November 2004. doi:10.1084/jem.20041185
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 9, 1145-1156
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The Role of CXCR4 in Maintaining Peripheral B Cell Compartments and Humoral Immunity

Yuchun Nie1, Janelle Waite1, Faraha Brewer1, Mary-Jean Sunshine2, Dan R. Littman2, and Yong-Rui Zou1

1 Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, NY 10032
2 Howard Hughes Medical Institute, Skirball Institute of Biomolecular Medicine, New York University Medical Center, New York, NY 10016

Address correspondence to Yong-Rui Zou, Dept. of Microbiology, Columbia University, 701 West 168th St., HHSC 1406, New York, NY 10032. Phone: (212) 305-2123; Fax: (212) 305-1468; email: yz2001{at}columbia.edu

The chemokine receptor CXCR4 is expressed in B cells at multiple stages of their development. CXCR4 function in humoral immunity has not been fully investigated. We have generated gene-targeted mice in which CXCR4 can be selectively inactivated in B cells and have shown that it is required for retention of B cell precursors in the bone marrow. CXCR4-deficient B cell precursors that migrated prematurely became localized in splenic follicles despite their unresponsiveness to CXCL13. Concomitantly, mature B cell populations were reduced in the splenic marginal zone and primary follicles, and in the peritoneal cavity in the mutant animals, as were T-independent antibody responses. In addition, aberrant B cell follicles formed ectopically in intestinal lamina propria around Peyer's patches. These findings establish an important role for CXCR4 in regulating homeostasis of B cell compartmentalization and humoral immunity.

Key Words: chemokine receptor • B lymphocytes • migration • plasma cell • Peyer's patches


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