Follicular dendritic cell-dependent adhesion and proliferation of B cells in vitro.
In response to an antigenic challenge, B cells proliferate in germinal centers within secondary lymphoid tissue. Specialized accessory cells, follicular dendritic cells (FDC), and T cells are necessary to drive this reaction. Indirect evidence suggests that FDC provide signals which not only induce B cell proliferation but can rescue B cells programmed to die by apoptosis. An in vitro system was developed to: 1) define the role of FDC and 2) identify molecules involved in this response. Activated, low density B cells and T cells were coisolated with FDC from immune mouse lymph nodes. Upon culturing, large cellular aggregates formed, composed of 1 to 3 FDC interdigitating between 30 to 90 B cells and 1 to 5 T cells. Many of these B cells were undergoing DNA synthesis. Depleting FDC or T cells from the cultures immediately stopped cluster formation and proliferation. Separating clustered vs nonclustered cells revealed that the FDC-associated population remained viable, whereas cells in suspension became apoptotic. The adhesion/activation molecules ICAM-1, LFA-1, and CD44 supported both cluster formation and proliferation. In addition, anti-class II and anti-kappa L chain mAb interfered dramatically with DNA synthesis. This model mimics many of the features of a germinal center and can be used to further study B cell activation, proliferation, and differentiation in vitro.
Kosco
M H
MH
Basel Institute for Immunology, Switzerland.
Pflugfelder
E
E
Gray
D
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001402:B-Lymphocytes / Q000502:physiology*; D002448:Cell Adhesion; D002470:Cell Survival; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016201:Receptors, Lymphocyte Homing / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology
D000911:Antibodies, Monoclonal; D016201:Receptors, Lymphocyte Homing