The immune system is composed of a number of leukocyte populations. Cell-cell interactions which occur between lymphoid cells are crucial in the expression of the functional potential of those cells. The interactions of two significant leukocyte populations, T and B lymphocytes, will be investigated in the proposed studies. It is hypothesized that only when B lymphocytes are in a well-defined state of activation can effective interaction with T lymphocytes occur.
Three specific aims will be addressed: 1) The function of activated and resting B lymphocytes will be compared with regard to their capacity to interact with T lymphocytes. T lymphocyte reactivity will be assessed in assays which measure response to self-Ia (autologous mixed leukocyte reaction), response to allogeneic Ia (allogeneic mixed leukocyte reaction) and response to self-Ia plus foreign antigen (antigen-induced T cell proliferation). B cells from normal subjects and from patients with chronic lymphocytic leukemia (representing a monoclonal population of resting B cells) will be activated with B cell mitogens and with anti-immunoglobulin antibody and compared to untreated B cells in the above assay systems. B cells will also be activated in vivo following tetanus toxoid immunization. B lymphoblastoid cell lines representing various stages of differentiation will also be used in these assays. 2) Several possible mechanisms of the augmented function of activated, compared with resting, B cells will be explored. The cell surface phenotype of activated B cells will be compared to that of resting cells. The appearance of B cell differentiation antigens on activated B cells will be studied and efforts made to associate such antigens with augmented T cell stimulatory function. A possible relationship between quantity of cell surface sialic acid residues and B cell stimulatory function will be sought. The importance of an intact antigen processing mechanism in the augmented activity of activated B cells will be studied. Finally, 3) the phenotype and function of the activated B cells found in patients with SLE will be compared to that of the in vitro activated B cells from normal subjects. A population of normal resting B cells which have the capacity to engage in appropriate interactions with T cells will be sought.
| Stohl, W; Crow, M K (1990) Inhibition by anti-CD2 monoclonal antibodies of anti-CD3-induced T cell-dependent B cell activation. Cell Immunol 130:257-70 |
| Crow, M K; Kushner, B; Jover, J A et al. (1989) Human peripheral blood T helper cell-induced B cell activation results in B cell surface expression of the CD23 (BLAST-2) antigen. Cell Immunol 121:99-112 |
