The role of functionally distinct helper T lymphocyte subpopulations in the inductionof human B cell differentiation

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Abstract
Human helper T lymphocytes can be dissected into two functionally distinct subpopulations based on expression of the CD45RA (2H4) or CD45R0 (UCHL‐1) surface antigens. While both subpopulations are able to induce equivalent levels of B cell activation and proliferation, only the CD4+CD45RA− subpopulation is capable of inducing B cell differentiation in pokeweed mitogen (PWM)‐stimulated cultures. To define the mechanism responsible for the dichotomy between induction of proliferation and differentiation by the two CD4+ subpopulations, we examined the abilities of the purified T cell subpopulations to produce lymphokine mRNA following T cell activation. Northern analysis revealed that both subpopulations produced interleukin (IL) 2 and interferon (IFN)‐γ mRNA following PWM activation. The CD4+CD45RA− subpopulation, however, produced higher levels of IFN‐γ mRNA and the CD4+CD45RA+ cells produced higher levels of IL 2 mRNA. Neither subpopulation elaborated detectable mRNA for IL 4, IL 5 or IL 6. Of greatest significance was that the addition of recombinant or T cell‐derived lymphokines could not compensate for the inability of the CD4+CD45RA+ subpopulation to induce B cell differentiation in PWM assays. Direct T‐B cell contact was required for the optimal induction B cell differentiation in these assays, suggesting that CD4+CD45RA+ T cells were deficient in their abilityto directly deliver the T cell‐B cell signals required for B cell differentiation. These results suggest that the differential abililty of the two subpopulations of CD4+ T cells to induce B cell differentiation does not result from differences inlymphokines elaborated, but may result from differences in their abilities to interact directly with B cells to initiate differentiation.