The Class II Molecule as a Signal Transducer to the B Cell: Cellular and Molecular Approaches
The ultimate function of B lymphocytes is the production and secretion of specific immunoglobulin (Ig). This process is regulated by interactions between cells, cell products, and antigen. Particularly significant are antigen-specific interactions between B and T helper (Th) lymphocytes. Activation of the Th cell in such interactions requires that an antigen-presenting cell, such as a macrophage, dendritic cell, or B cell, present antigen to the Th cell in association with molecules encoded by genes of the class II region of the major histocompatibility complex (MHC). The function of class II antigens in T cell activation has been the subject of intense investigation in recent years (Schwartz, 1985; Germain and Malissen, 1986; Guillet et. al., 1987). There is little understanding, however, of the role of the B cell class II molecule in transmitting a differentiative signal to the B cell itself. This question has been technically difficult to approach, since all antigen-presenting cells express class II antigens. Thus, the unavoidable contamination of uncloned B cells with at least a small percentage of macrophages makes the use of such cells to define the signaling function of B cell Ia problematic. Although long-term culture of untransformed B cells has met with some success (Braun et. al., 1986; Pike and Nossal, 1986), such cell lines are not yet widely available. An alternative approach employs transformed, immortal B cell lines to study the process of B cell differentiation (Arnold et. al., 1986). A major limitation in the study of many B cell tumors is that the specificity of the Ig which they produce is unknown. Therefore, it is difficult to use them to study antigen-specific interactions. However, several clones of transformed murine B cells have been characterized which bear Ig of defined antigenic specificity and are responsive to immunoregulatory signals (Bishop et. al., 1986a). The CH series of murine B cell lymphomas has proven useful in studying B cell differentiation (Haughton et. al., 1986; Bishop and Haughton, 1987).
KeywordsMajor Histocompatibility Complex Mouse Mammary Tumor Virus Mycophenolic Acid Differentiative Signal Cell Antigen Recognition
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