The regulation of T cell-dependent antibody formation in vitro by CD40 ligand and IL-2.
Our study demonstrates the central role for the murine CD40 ligand and IL-2 in contact-dependent T cell help for Ag-specific primary antibody responses in vitro. Helper T cell clones were found to express CD40 ligand after activation with CD3 mAb. Membrane-bound recombinant CD40 ligand expressed on fixed CV1/EBNA cells had similar B cell-activating properties as T cell clones that had been activated and then fixed. These activities include the induction of B cell proliferation, induction of polyclonal secretion of multiple Ig isotypes in a cytokine-dependent manner, and induction of Ag-specific antibody responses by purified B cells. The induction of polyclonal Ig secretion by the recombinant CD40 ligand required IL-4 and IL-5 although optimal Ag-specific antibody formation required IL-2. Finally, soluble CD40.Fc inhibited the induction of Ag-specific antibody responses by fixed, activated Th cell clones. The requirement for both CD40 ligand and IL-2 for induction of Ag-specific antibody responses was mediated, in part, by the induction of B cell IL-2R expression by CD40 ligand. We conclude that the interaction of CD40 on B cells with its ligand on activated T cells is an integral event in the early activation of B cells to grow and differentiate to antibody formation.
Grabstein
K H
KH
Department of Immunology, Immunex Research and Development Corporation, Seattle, WA 98101.
Maliszewski
C R
CR
Shanebeck
K
K
Sato
T A
TA
Spriggs
M K
MK
Fanslow
W C
WC
Armitage
R J
RJ
D000818:Animals; D000917:Antibody Formation; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens; D023201:CD40 Ligand; D005260:Female; D007376:Interleukin-2 / Q000276:immunology*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D023201:CD40 Ligand