Arrest of B lymphocyte terminal differentiation by CD40 signaling: mechanism for lack of antibody-secreting cells in germinal centers.
Despite extensive research, the role of CD40 signaling in B cell terminal differentiation remains controversial. Here we show that CD40 engagement arrests B cell differentiation prior to plasma cell formation. This arrest is manifested at a molecular level as a reduction in mRNA levels of secretory immunoglobulin gene products such as mu(s) and J chain as well as the loss of the transcriptional regulator BLIMP-1. Furthermore, the inhibition of B cell differentiation by CD40 engagement could not be overcome by either mitogens or cytokines, but could be reversed by antibodies that interfere with the CD40/gp39 interaction. These data suggest that secretory immunoglobulin is not produced by B cells that are actively engaged by gp39-expressing T cells.
Randall
T D
TD
Trudeau Institute, Saranac Lake, New York 12983, USA.
Heath
A W
AW
Santos-Argumedo
L
L
Howard
M C
MC
Weissman
I L
IL
Lund
F E
FE
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand; D002454:Cell Differentiation / Q000276:immunology; D018920:Coculture Techniques; D018858:Germinal Center / Q000166:cytology / Q000276:immunology*; D006801:Humans; D008024:Ligands; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012097:Repressor Proteins; D015398:Signal Transduction / Q000276:immunology*; D014157:Transcription Factors / Q000276:immunology
D000906:Antibodies; D019013:CD40 Antigens; D008024:Ligands; D008562:Membrane Glycoproteins; C513258:Prdm1 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; C087042:PRDM1 protein, human; D023201:CD40 Ligand; D000074462:Positive Regulatory Domain I-Binding Factor 1