CD40-activated surface IgD-positive lymphocytes constitute the long term IL-4-dependent proliferating B cell pool.
In vitro, B cells undergo long term proliferation when triggered through their CD40 surface molecule and in the presence of IL-4. Here, we show that cells that proliferate in this culture system lose their germinal center (GC) features and acquire or maintain non-GC markers. When separated by the magnetic cell separation system, both sIgD+ and sIgD- B cells can proliferate in this culture system, sIgD+ B cells exhibiting a higher rate of growth than sIgD- cells. Simultaneous flow cytometric measurement of sIgD and DNA content revealed that B lymphocytes can keep their sIgD after entry into cell cycle. Experiments using G8 Id-positive B lymphocytes allowed us to follow the evolution of sIgD+ and sIgD- cells in a reconstituted B cell population. Long term proliferating cells are sIgD+/sIgM(+)-derived B lymphocytes whereas the initial sIgD-/sIgM- cells are lost. Taken together, these data show that anti-CD40 + IL-4 activated sIgD+ B blasts express non-GC characteristics and that sIgD+ B cells preferentially proliferate in the CD40 system. The possible in vivo role of IL-4 + CD40 signaling is discussed.
Galibert
L
L
Schering-Plough, Laboratory for Immunological Research, Dardilly, France.
Durand
I
I
Banchereau
J
J
Rousset
F
F
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology / Q000502:physiology*; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D019013:CD40 Antigens; D002453:Cell Cycle / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D007072:Immunoglobulin D / Q000032:analysis*; D015847:Interleukin-4 / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology; D014066:Palatine Tonsil / Q000166:cytology; D011947:Receptors, Antigen, B-Cell / Q000032:analysis*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D007072:Immunoglobulin D; D011947:Receptors, Antigen, B-Cell; D015847:Interleukin-4