A significant proportion of normal resting B cells are induced to secrete immunoglobulin through contact with anti-receptor antibody-activated helper T cells in clonal cultures.
This report describes single-cell techniques to address the nature of a cellular interaction in which activated T lymphocytes stimulate small resting B cells to develop into antibody-forming cell clones in the absence of any surface immunoglobulin ligand or an antigen bridge. The cloned T helper cell line E9.D4 was stimulated with the anti-V beta 8 antibody F23.1 bound to the plastic of Terasaki 10-ul culture wells. When an excess of T helper lymphocytes was used (1,000 X-irradiated or 600 unirradiated, stimulated E9.D4 cells), 10-25% of B cells responded by antibody formation as judged by an enzyme-linked immunosorbent assay performed after 5 days of culture. When one of a very small number of B cells were present, the rate-limiting step to antibody-forming cell formation was the number of T cells present. Far fewer T cells sufficed for stimulation when culture trays were tilted to force T and B cells into proximity at the sulcus formed at the bottom edge of the culture wells. When T cell numbers were limiting, unirradiated T cells out-performed irradiated T cells. Some cell clones held for 7 days switched to IgG antibody production. E9.D4 supernatants were virtually ineffective in causing B cell stimulation, even when 3T3 filler cells were added to support cultures. The results suggest that cell contact, and perhaps conjugate formation, with a strongly activated T cell can cause changes in the adjacent resting B cells akin to those of Ig receptor cross-linking, following which a lymphokine flux (even one not involving IL 4 and 5) promotes antibody-forming cell development.
Riedel
C
C
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Owens
T
T
Nossal
G J
GJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002450:Cell Communication; D002460:Cell Line; D007136:Immunoglobulins / Q000378:metabolism*; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008222:Lymphokines / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008808:Mice, Inbred CBA; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism / Q000528:radiation effects
D000911:Antibodies, Monoclonal; D007136:Immunoglobulins; D008222:Lymphokines; D011948:Receptors, Antigen, T-Cell