B cell differentiation centers on changes in immunoglobulin (Ig) gene expression--the production of Ig with high antigen-binding avidity and heavy chain isotype suitable to elicit various physiologic responses to foreign antigen. In the proposed project, the structural features of Ig gene expression will be analyzed in unique, long-term B lymphocyte cell lines (B-Lyl cells) and antigen-specific subclones. In respone to conven- tional stimuli (anti-IgM and lymphokines), these cells initiate high-rate IgM secretion, production of """"""""mature"""""""" heavy chain isotypes (class switching), and heavy chain class switching. Consequently, the molecular events related to Ig gene expression can be analyzed in these cells as an inducible, ongoing process. Using recombinant DNA techniques, the molecular basis for the changes in Ig gene expression will be determined: sequential DNA rearrangements, and structural and quantitative changes in mRNA species. Screening methods for somatic mutation will also be evaluated. These molecular events may then be used to more precisely characterize the regulatory influence of various T lymphocyte subclasses, macrophages, and their soluble product. B-Lyl cells are also notable for their similarity by surface phenotye to a minor B cell population believed to account for the polyclonal Ig production in genetic models of murine SLE. In the future, comparison of B-Lyl cell lines derived from """"""""normal"""""""" and """"""""lupus"""""""" strains may clarify the mechanism of abnormal Ig production in this disease model.
| Felsher, D W; Rhim, S H; Braun, J (1990) A murine model for B-cell lymphomagenesis in immunocompromised hosts: natural killer cells are an important component of host resistance to premalignant B-cell lines. Cancer Res 50:7050-6 |
| Braun, J; Krall, W J; Clark, M E et al. (1988) Inducible Ig heavy chain switching in an IgM+ Ly-1 B cell line. Evidence for a state of switch commitment. J Mol Cell Immunol 4:105-19 |
| Braun, J; Citri, Y; Baltimore, D et al. (1986) B-Ly1 cells: immortal Ly-1+ B lymphocyte cell lines spontaneously arising in murine splenic cultures. Immunol Rev 93:5-21 |
