Direct effect of interleukin 2 on the differentiation of human B cells which have not been preactivated in vitro

Unfractionated as well as small and large human tonsillar B cells were found to differentiate in the presence of recombinant interleukin 2 (IL2) without requiring an in vitro preactivation signal. These cell suspensions did not contain detectable T cells, monocytes or natural killer cells both at the initiation and the termination of cultures, and did not respond to the T cell-dependent polyclonal B cell activator pokeweed mitogen. They contained very few Tac antigen-bearing cells (less than 2.5%) at the beginning and at the termination of the cultures in the absence of IL2. In the presence of IL2, only a minimal increase in the number of Tac antigen-bearing cells was noted. The observed differentiation was not due to the effects of contaminating T cells, since cultures purposely contaminated with up to 5% of T cells did not contain greater amounts of IgM, IgG or IgA than cultures without T cells added back. Furthermore, when T cells were present at a ratio of 1 T cell per 9 B cells, the production of IgM was decreased. Taken together, these data support the hypothesis that (a) B cell differentiation in response to IL2 may occur in the absence of in vitro preactivation, and in this case cannot be related to the expression of Tac antigen on the B cell surface; (b) it is not due to helper effects of very low numbers of T cells which might contaminate the B cell suspensions; and (c) it most likely results from a direct effect of IL2 on B cells themselves. The data also point out the fact that, in the presence of IL2, T cells may trigger inhibitory effects on IL2-induced B cell differentiation rather than provide helper signals.