The supernatants of activated type 2 T helper cell (Th2) clones are capable of inducing polyclonal proliferation and immunoglobulin (Ig) secretion by heterogenous unprimed B cell populations. Studies employing recombinant lymphokines demonstrated that IL5 is sufficient to induce these responses. Recombinant IL5 stimulation also results in the appearance of a phenotypically novel B cell population which expresses high densities of Pgp-l (CD44) and relatively low densities of B220 (CD45) and Ia. Cell fractionation experiments demonstrated that the B cell subpopulation expressing this novel phenotype mediates nearly all of the proliferative and immunoglobulin secretory activity of the activated B cell populations. In addition, the CD44 expressed by these cells is capable of mediating binding to the extracellular matrix material hyaluronic acid (HA), indicating a potential role for CD44 in regulating the trafficking of activated B cells in vivo. The CD44 molecules expressed on IL5-stimulated B cells migrate with a lower molecular weight than does CD44 expressed by control B cells, reflecting differential glycosylation. A series of mAb was generated by immunizing rats with activated mouse B cells. One of these mAb (CL7) reacts by flow cytometry with a subpopulation of B cells activated with stimuli including LPS or anti-Ig. This mAb precipitates a 29-31 KDa molecule from activated but not resting B cells. This appears to represent a previously undescribed activation molecule. To establish a system for the study of Th cell-B cell interaction at a single cell level, responses were generated using Ig transgenic B cells and cloned Th cells. Highly efficient hapten-specific responses were generated.