Requirement for noncognate interaction with T cells for the activation of B cell immunoglobulin secretion by IL-2.
The mechanism whereby noncognate contact with activated IL-2-producing Type 1 helper T cells (TH1) induces B cell activation was examined. Small resting B cells from C57B1/6 mice were cultured, in the absence of any ligand for surface Ig, with irradiated cells of the hapten-specific, CBA-derived, F23.1+ TH1 clone E9.D4 in F23.1 (anti-T cell receptor V-beta 8)-coated microwells. This induced polyclonal B cell activation to enter cell cycle (thymidine incorporation) at 2 days and to secrete immunoglobulin at 5 days. An anti-IL-2 mAb (S4B6) inhibited antibody production completely. Anti-IL-2 did not inhibit either LPS-induced B cell responses, or T cell activation (measured as IL-3 secretion). Anti-IL-2 receptor (anti-Tac) mAbs also inhibited T-dependent B cell responses, without affecting LPS responses. An anti-IFN-gamma mAb partially inhibited Ig secretion, without affecting entry into cycle. LPS responses or T cell activation. Other antibodies (anti-IL-3, IL-4, IL-5, Thy-1.2, CD5) were not inhibitory. After 2 days of culture with F23.1-activated T cells, B cells appeared to have become responsive to IL-2, in that they could be driven to immunoglobulin production by the addition of IL-2. Flow cytometry showed no expression by these B cells of 55-kDa (Tac) IL-2 receptors. Also, rigorous removal of T cells from 2-day cocultures prevented the response to IL-2, and readdition of T cells restored it. Because the reconstituted responses were inhibited both by anti-IL-2 and by anti-Tac, IL-2 must have acted indirectly, via the T cells that were present in these cultures. Continued contact with T cells was therefore necessary for the progression of B cells to antibody secretion.
Owens
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Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D007136:Immunoglobulins / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000494:pharmacology* / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*
D000911:Antibodies, Monoclonal; D007136:Immunoglobulins; D007376:Interleukin-2; D015375:Receptors, Interleukin-2