AbstractA number of human B lymphoblast cell lines were tested to find a suitable model for induction of immunoglobulin‐secreting cells (ISC) by T cell replacing factor (TRF). Partially purified TRF was size fractionated from the conditioned medium of irradiated (1000 rds) human spleen cells stimulated with pokeweed mitogen. IgM line SKW 6 showed high levels of TRF‐stimulated immunoglobulin secretion and was chosen for cloning experiments. Clone 11 had a very low level of ISC with or without TRF (less than 0.1% ISC). Clone 4 had low background numbers of ISC (0.2%) and showed the highest degree of stimulation by TRF (to 6% IFC). High secreting clone 8‐2 (6%) was not stimulated significantly by TRF. These clones had the same HLA‐DR antigens, and their levels of ISC and sensitivity to TRF were relatively stable over three months of observation. The TRF preparation also had strong helper activity for normal peripheral blood B cell differentiation. TRF activity for both normal B cells and clone 4 cell line was absorbed by all 3 clones, but not by a pre‐B line. This suggests that the effector molecules for normal B cell and cell line differentiation were the same. The three typical clones corresponding to nonresponding, responding, and high rate‐secreting B cells provide basic models for analyzing B cell receptors for TRF and the biochemical effects of TRF during B cell diffe