Regulation of Growth and Differentiation in B Cell Clones and Hybrids

Abstract

Analysis of the molecular events which occur during specific B cell activation or inactivation has been hampered by the rare frequency of antigen-specific B cells, as well as by the heterogeneity of B cell subpopulations and stages of differentiation. An initial approach to the solution of this dilemma is to enrich for antigen-specific lymphocytes. The purification of B cells of a single hapten-specificity has, indeed, been possible for a number of years (1). However, such enrichment procedures do not overcome the heterogeneity which exists in B cells of a single specificity. The ability to clone hapten-specific B cells and/or hybridize them to an appropriate tumor cell would resolve many of these difficulties, assuming that the “normal” B cell phenotype can be retained. In analogy to the technology of T cell cloning, which is abundantly apparent at the present meeting, clones of hapten specific B cells are now being prepared. In contrast to T cell cloning, however, it is not yet possible to repeatedly stimulate B cells with specific antigen in the absence of terminal differentiation to antibody secreting cells. The present report describes the current state of the art with regard to B cell cloning technology to yield functional short-term hapten-specific clones as well as long-term hapten-specific inducible hybrids. We will focus on the kinds of B cell clones which we are able to grow and detect in terms of differential function and will begin an analysis of the regulation of the growth and/or differentiation of such clones by antigen, mitogenic growth potentiators, and cellderived factors. Finally, the use of cell hybridization technology will be described. This yielded several B cell tumor hybrids, one of which has been studied in detail. The regulation of the growth of such a hybrid by T cell products will be introduced.