J. Exp. Med., Volume 189, Number 9, May 3, 1999 1413-1423

Interleukin 9-induced In Vivo Expansion of the B-1 Lymphocyte Population

By Anne Vink,^* Guy Warnier,^* Frank Brombacher, and Jean-Christophe Renauld^*

From the ^* Ludwig Institute for Cancer Research, Experimental Medicine Unit, University of Louvain, B-1200 Brussels, Belgium; and the  University of Cape Town, 7925 Cape Town, South Africa

The activity of interleukin (IL)-9 on B cells was analyzed in vivo using transgenic mice that constitutively express this cytokine. These mice show an increase in both baseline and antigen-specific immunoglobulin concentrations for all isotypes tested. Analysis of B cell populations showed a specific expansion of Mac-1⁺ B-1 cells in the peritoneal and pleuropericardial cavities, and in the blood of IL-9 transgenic mice. In normal mice, the IL-9 receptor was found to be expressed by CD5⁺ as well as CD5 B-1 cells, and repeated injections of IL-9 resulted in accumulation of B-1 cells in the peritoneal cavity, as observed in transgenic animals. Unlike other mouse models, such as IL-5 transgenic mice, in which expansion of the B-1 population is associated with high levels of autoantibodies, IL-9 did not stimulate the production of autoantibodies in vivo, and most of the expanded cells were found to belong to the B-1b subset (IgM⁺Mac-1⁺CD5). In addition, we found that these IL-9-expanded B-1b cells do not share the well-documented antibromelain-treated red blood cell specificity of CD5⁺ B-1a cells. The increase of antigen-specific antibody concentration in immunized mice suggests that these B-1 cells are directly or indirectly involved in antibody responses in IL-9 transgenic mice.

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