Effect of Azathioprine on in Vitro Antibody Response. Differential Effect on B Cells Involved in Thymus-dependent and Independent Responses

The effect of azathioprine (Az) on the primary in vitro antibody response of mouse spleen cell cultures has been studied. The response towards T cell-dependent antigens is suppressed by low Az concentrations (50% inhibition by 10(-2) mug/ml and 100% suppression by 10(-1) mug/ml). The same pattern is observed when Az addition is delayed until day 2, but the suppression is absent or partial when Az is added on day 3. In the early period (day 0 to day 1) the effect of Az is reversible upon addition of an excess of purine nucleosides. In contrast, the response to a T cell-independent antigen (TNP-T4) is relatively insensitive to Az, since 100-fold higher drug concentrations are required to obtain an inhibition. With the assumption that T helper cells are likely to be highly sensitive to Az, the effect of low Az concentrations on the other two cell populations involved in T cell-dependent responses has been evaluated. Adherent cells appear unaffected. In contrast, the B-cell response is markedly sensitive to Az, as shown by the effect of Az on the response of nude mouse cells to a T cell-dependent antigen in the presence of T-cell products, either specific or non-specific. On the other hand, the B-cell response to mitogens is resistant to az. Thus, Az has a differential effect on B-cell response according to the thymus dependency of the antigen. This may suggest the existence of two pathways for B-cell activation or two different B-cell subpopulations.