Cross-linking of antigen receptor via Ig-beta (B29, CD79b) can induce both positive and negative signals in CD40-activated human B cells.
Antigen-dependent activation of B lymphocytes is mediated through surface immunoglobulins and their associated molecules Ig-alpha (CD79a, Mb1) and Ig-beta (CD79b, B29). Here we show that an antibody directed against the extracellular part of human Ig-beta can, when cross-linked by CD32-transfected L cells, induce an IL-2-dependent proliferation of tonsil B cells. With the use of L cells stably transfected with both CD32 and CD40L, anti-Ig-beta activation of B cells was combined with CD40 triggering, an important component of the T cell-dependent B cell activation. This dual cellular activation resulted in two different phases, with initially synergistic proliferative effects, both without and with IL-2 or IL-10. Then, after 5-6 days of culture, cells stimulated with both anti-Ig-beta and CD40L underwent massive cell death, in contrast to B cells activated with CD40L alone. Cell death was not prevented by the addition of IL-2 or IL-10, but was prevented by the addition of IL-4. These results are discussed in the context of positive and negative selection of mature B cells.
Van Kooten
C
C
Laboratory for Immunological Research, Schering-Plough, Dardilly, France.
Galibert
L
L
Seon
B K
BK
Garrone
P
P
Liu
Y J
YJ
Banchereau
J
J
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D001402:B-Lymphocytes / Q000502:physiology*; D019013:CD40 Antigens / Q000502:physiology*; D051925:CD79 Antigens; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*
D015703:Antigens, CD; D019013:CD40 Antigens; D051925:CD79 Antigens; C497883:CD79B protein, human; C497884:Cd79b protein, mouse; D011947:Receptors, Antigen, B-Cell; D015847:Interleukin-4