We find that efficient activation of B cells with LPS + DxS requires the """"""""help"""""""" of accessory cells, typically radioresistant, adherent cells derived from the culture of cells of lymphoid organs. Using limiting dilution approaches and a special repartitioning protocol, we have measured the freequency of the special adherent cell that make the factor necessary for B cells responding to mitogen. Frequencies approach 3% of adherent cells. In addition to naturally occurring accessory cells, we found that several macrophage-like cell lines are also capable of showing accessory cell activity and one line, WEHI-3, elaborates a factor which replaces accessory cells. In addition to """"""""helper"""""""" adherent accessory cells, we observed adherent, radioresistant """"""""suppressor"""""""" cells which were found in peritoneal cell populations. We propose surveying a variety of natural sources of accessory cells and determining the fraction which """"""""help"""""""" or """"""""hinder"""""""" mitogen activation of B lymphocytes. We will characterize, purify and isolate each of the adherent cell populations which help, hinder or have no influence on activation. We will also compare those adherent cells active with B cells to those necesssary for the mitogen activation of T lymphocytes. When the cells that perform the above activities are identified, we will attempt the interconversion of these functional cell types by use of pharmacologic mediators, adjuvants (such as LPS and polyanions) and lympokines elaborated by T cells or B cells. We propose to characterize the mechanism of action of the suppressor accessory cell - does it act by cell contact or release of suppressive factors? We also propose determining if all B cells equally require accessory activity and if different stages of B cells undergoing activation also require accessory activity. Further, are they equally sensitive to suppressor effects. We are interested in uncovering, using quantitative biological procedures, the mechanism by which accessory cells of the macrophage series affect B cell activation and subsequent clonal expansion and differentiation.
| Hoot, G P; Harrod, F A; Kettman, J R (1991) Histology of transplantable murine epithelial tumors infiltrated with immature T lymphocytes: neoplastic analogues of the thymus. Thymus 17:81-95 |
