The nude mutation results in impaired primary antibody repertoire.

We have studied the effect of the nude mutation and/or T lymphocytes on the development of V gene germ-line repertoire in neonatal athymic (nu/nu) and euthymic (+/nu) littermates. A total of 2.35 x 10(6) and 1.47 x 10(6) B lymphocyte clones from nu/nu and +/nu neonates, respectively, were examined for the expression of select VH (J558, J606, S107, 36-60, 7183 and Q52) and Vx (1, 2, 8 and 9) gene families as well as VH (J558, S107) + Vx (1, 9) associations. Data showed that the nude mutation, whether homozygous or heterozygous, significantly affects VH and Vx gene expression as well as VH and Vx pairings and, thus, provide evidence for a defective development of B cell repertoire in both athymic nude (nu/nu) and euthymic (+/nu) mice. In addition, an analysis of 3.34 x 10(6) B lymphocyte clones from adult C57BL/6 mice showed non-stochastic association between VHJ558 + Vx1 gene families that suggests restrictions on clonal population in order to maintain homeostasis in the immune system. Studies outlined here, therefore, describe an hitherto unknown defect in the development of B lymphocyte repertoire as a result of the nude mutation which is independent of thymic dysgenesis.