The objective of this study was to determine whether certain membrane markers on B cells are involved with receipt of a T-cell helper signal. The helper factor, derived from an allogeneic supernatant, is antigen non-specific, non-Ia bearing and, thus, akin to T-cell replacing factor (TRF). The markers are murine differentiation antigens (MDAs) that are detected by two types of isogeneic lymphocyte culture (ILC). In Type 1 ILC replication of neonatal thymic cells is caused by MDA-1 and MDA-2 whereas in Type 2 ILC blastogenesis of adult lymph node T cells is triggered by MDA-2. Bone marrow (BM) cells, known to lack both MDAs, were used to reconstitute X-irradiated CBA/J mice and cells that homed to the spleen were examined by ILC at intervals to determine when the markers arose. In addition, purified splenic B cells from the reconstituted mice were exposed in vitro to sheep erythrocytes and TRF to determine their imimmunological capacity. Spleen cells obtained from mice 12 weeks after reconstitution with BM cells were shown to have acquired MDA-1 and to have the capacity, following interaction with TRF, to produce the maximum number of cells synthesizing IgM and IgG antibodies to SRBC. Spleen cells examined 5–6 weeks following reconstitution expressed MDA-2 but were unresponsive to TRF. BM-derived cells matured earlier in the presence of splenic T cells; they expressed MDA-1 and were able to interact with TRF at 5–6 weeks. On the other hand, BM-derived cells that acquired MDA-2 at an earlier, 2 week interval still remained unable to interact with TRF. These correlations of marker appearances with cellular function suggest MDA-1 may be a receptor for TRF.