Role of antigen in the B cell response. Specific antigen and the lymphokine IL-5 synergize to drive B cell lymphoma proliferation and differentiation to Ig secretion

Abstract

CH12 tumor B cells specific for SRBC require SRBC as Ag and the lymphokine IL-5 (formerly known as BCGFII) for optimal proliferation and differentiation to Ig-secreting cells. Lysed SRBC and IL-5 purified to homogeneity synergize markedly, especially at low B cell densities. A sizable proportion of CH12 cells differentiate into Ig-secreting plaque-forming cells when low numbers of the B lymphoma cells (100 to 3000) are cultured with Ag and IL-5. IL-2 or IL-4 have no effects. Intact SRBC or lysed SRBC are equally effective as sources of Ag. Even in the presence of the mitogens LPS and dextran sulfate, there is a striking requirement for Ag for both proliferation and differentiation at low B cell density. Because of the low cell numbers used, the results strongly suggest that the effects of Ag and lymphokine are directly on the B cell. The cell surface phenotype of the CH12 lymphoma and the kinetics of their response suggest that CH12 B cells have the characteristics of activated B cells. Thus, it appears that Ag binding to surface Ig gives a direct signal to at least some B cells that is critical in the later phases of the B cell response after initial activation during which proliferation and differentiation to Ig secretion occur and that the lymphokine IL-5 costimulates with Ag to mediate this phase of the response.