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Enforced bcl-x_L Gene Expression Restored Splenic B Lymphocyte Development in BAFF-R Mutant Mice¹

Ian J. Amanna^*, Jennifer P. Dingwall and Colleen E. Hayes^2,*

Departments of ^* Biochemistry and Genetics, University of Wisconsin, Madison, WI 53706

The TNFR family member BAFF-R facilitates peripheral B cell development, although it is unclear whether it promotes survival of B cells, or also initiates a differentiation program. We show that disruption of the BAFF-R encoding gene Tnfrsf13c in strain A/WySnJ mice causes a progressive decline in peripheral B cell numbers, beginning at the transitional 1 developmental stage and continuing through the mature peripheral B cell stage. Bcl-x_L overexpression in A/WySnJ B cells decreased the turnover of transitional B cells, as determined by 5-bromo-2'-deoxyuridine labeling, and restored follicular B cell development. We conclude that the mutant A/WySnJ allele of Tnfrsf13c can be complemented through the survival signal provided by Bcl-x_L.

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