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Induced Expression of Murine 2a by CD40 Ligation Independently of IFN-¹

John T. Collins^*, Jian Shi^*, Bryna E. Burrell^,, D. Keith Bishop^*, and Wesley A. Dunnick^2,*

^* Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109; Department of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109; and Graduate Program in Immunology, University of Michigan Medical School, Ann Arbor, MI 48109

IgG2a, with 2a H chains, is important for protection against viruses and other intracellular pathogens. Although a large portion of IgG2a expression is dependent upon IFN-, some germline transcription and switch recombination to the murine 2a H chain gene expression are independent of IFN-. We found that agonistic anti-CD40 Abs injected into IFN--deficient mice induce a >200-fold increase in the amount of serum Ig2a, while other Ig isotypes are increased by 16-fold or less. In vitro, ligation of CD40 on B cells, without the addition of other B cell activators or cytokines, results in germline transcription and switch recombination that are largely restricted to the 2a gene. These results suggest that some immune responses to infectious agents can result in large amounts of IgG2a expression through ligation of CD40, without the expression of IFN- by Th1 or other cells.

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 the National Institutes of Health (R01 CA39068 to W.A.D. and RO1 AI061469 to D.K.B.) and by the Midwest Affiliate of the American Heart Association (0151127Z to W.A.D.). B.E.B. was supported by the Research Training in Experimental Immunology Grant (T32AI007413).

² Address correspondence and reprint requests to Dr. Wesley A. Dunnick, Department of Microbiology and Immunology, University of Michigan Medical School, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0620. E-mail address: wesadunn{at}umich.edu

³ Abbreviations used in this paper: CD40L, CD40 ligand; IRF, IFN regulatory factor.

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