Autocrine models of B-lymphocyte growth. I. Role of cell contact and soluble factors in T-independent B-cell responses.
The requirements for triggering human B cells to DNA synthesis by T-independent polyclonal activators were examined. Optimal S phase entry of purified resting B cells infected with Epstein-Barr virus (EBV) or confronted with killed particles of Staphylococcus aureus Cowan Strain I (SAC) required a high density of cells in culture. Experiments varying culture vessel geometry and culture volumes revealed that the initial limiting quantity was a soluble activity generated in the B-cell cultures. A parallel observation was noted in the requirements for the sustained growth of EBV-transformed lymphoblasts. Autostimulatory soluble factors harvested from such cultures were able to augment DNA synthesis in low density cultures of resting cells triggered by EBV or SAC. Below a critical cell number, however, soluble factors by themselves, were not sufficient either for supporting primary B-cell responses or for maintaining the proliferation of transformed lymphoblasts. By employing conditions which encouraged cell contact it was found that a second, non-harvestable factor requiring cell proximity for its action was also necessary to promote B-cell growth. The implications of these findings for autocrine and paracrine models of B-cell activation are discussed.