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The Role of B Cells in the Development of CD4 Effector T Cells during a Polarized Th2 Immune Response¹

Qian Liu^*, Zhugong Liu^*, Cristina T. Rozo^*, Hossein A. Hamed^*, Farhang Alem^*, Joseph F. Urban, Jr. and William C. Gause^2,*

^* Department of Medicine, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103; and Nutrient Requirements and Functions Laboratory, Beltsville Human Nutrition Research Center, U.S. Department of Agriculture, Beltsville, MD 20705-2350

Previous studies have suggested that B cells promote Th2 cell development by inhibiting Th1 cell differentiation. To examine whether B cells are directly required for the development of IL-4-producing T cells in the lymph node during a highly polarized Th2 response, B cell-deficient and wild-type mice were inoculated with the nematode parasite, Nippostrongylus brasiliensis. On day 7, in the absence of increased IFN-, IL-4 protein and gene expression from CD4 T cells in the draining lymph nodes were markedly reduced in B cell-deficient mice and could not be restored by multiple immunizations. Using a DO11.10 T cell adoptive transfer system, OVA-specific T cell IL-4 production and cell cycle progression, but not cell surface expression of early activation markers, were impaired in B cell-deficient recipient mice following immunization with N. brasiliensis plus OVA. Laser capture microdissection and immunofluorescent staining showed that pronounced IL-4 mRNA and protein secretion by donor DO11.10 T cells first occurred in the T cell:B cell zone of the lymph node shortly after inoculation of IL-4^–/– recipients, suggesting that this microenvironment is critical for initial Th2 cell development. Reconstitution of B cell-deficient mice with wild-type naive B cells, or IL-4^–/– B cells, substantially restored Ag-specific T cell IL-4 production. However, reconstitution with B7-1/B7-2-deficient B cells failed to rescue the IL-4-producing DO11.10 T cells. These results suggest that B cells, expressing B7 costimulatory molecules, are required in the absence of an underlying IFN--mediated response for the development of a polarized primary Ag-specific Th2 response in vivo.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Grant AI31678 from the National Institutes of Health.

² Address correspondence and reprint requests to Dr. William C. Gause, Department of Medicine, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, Newark, NJ 07103. E-mail address: gausewc{at}umdnj.edu

³ Abbreviations used in this paper: DC, dendritic cell; LCM, laser capture microdissection; CLN, cervical lymph node; PI, proliferation index; WT, wild type; Nb, Nippostrongylus brasiliensis; CD62L, CD62 ligand.

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