CD77: an antigen of germinal center B cells entering apoptosis.
We have previously reported that a neutral glycolipid (globotriosylceramide; Gb3) was specifically expressed on Burkitt's lymphoma cells and on a subset of germinal center tonsillar B lymphocytes. Recently the Gb3 molecule was recognized as a new B cell differentiation antigen and now defines the CD77 cluster. Here we report an extensive phenotypic and functional characterization of the tonsillar CD77+ B lymphocytes. These cells have a low buoyant density and are thus purified using a Percoll gradient. They express various B cell antigens such as CD19, CD20, CD21, CD22 and CD40, as well as the adhesion molecules LFA-1, LFA-3 and CD44. They are positive for surface IgM and negative for surface IgD. Although these results suggest a phenotype of activated B cells, the CD77+ cells are negative for the classical activation antigens: CD23 (the low-affinity Fc receptor for IgE), CD25 [the interleukin (IL) 2 receptor alpha chain] and CD71 (the transferrin receptor). Proliferation and protein synthesis of CD77+ cells was measured after stimulation with a range of mitogens and IL. None of the agents tested are able to induce proliferation and protein synthesis with the exception of a combination of recombinant IL 4 plus anti-CD40 antibody. When examined by electron microscopy, CD77+ B lymphocytes present a morphology similar to that of cells undergoing programmed cell death, also called apoptosis (i.e. chromatin condensation, nuclear fragmentation, membrane blebbing). As shown by direct examination of DNA, these CD77+ cells are indeed in the process of apoptosis. Treatment of the CD77+ cells by recombinant IL 4 and anti-CD40 antibody prevents apoptosis. All these results suggest that the CD77 molecule defines a B lymphocyte maturation pathway, specific for germinal center, where the cells undergo programmed cell death.
Mangeney
M
M
Laboratoire d'Immuno-Biologie des Tumeurs, CNRS URA 1156, Institut Gustave Roussy, Villejuif, France.
Richard
Y
Y
Coulaud
D
D
Tursz
T
T
Wiels
J
J
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology* / Q000648:ultrastructure; D019013:CD40 Antigens; D002469:Cell Separation; D002470:Cell Survival; D004247:DNA / Q000378:metabolism; D006017:Glycolipids / Q000032:analysis; D006801:Humans; D008213:Lymphocyte Activation; D010641:Phenotype; D014176:Protein Biosynthesis; D016201:Receptors, Lymphocyte Homing / Q000502:physiology; D014281:Trihexosylceramides / Q000032:analysis / Q000502:physiology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D006017:Glycolipids; D016201:Receptors, Lymphocyte Homing; D014281:Trihexosylceramides; C018549:globotriaosylceramide; D004247:DNA