bcl-2 transgene expression inhibits apoptosis in the germinal center and reveals differences in the selection of memory B cells and bone marrow antibody-forming cells
Details
Publication Year 2000-02-07, Volume 191, Issue #3, Page 475-484
Journal Title
JOURNAL OF EXPERIMENTAL MEDICINE
Publication Type
Journal Article
Abstract
Immunization with T cell-dependent antigens generates long-lived memory B cells and antibody-forming cells (AFCs). Both populations originate in germinal centers and, predominantly, produce antibodies with high affinity for antigen. The means by which germinal center B cells are recruited into these populations remains unclear. We have examined affinity maturation of antigen-specific B cells in mice expressing the cell death inhibitor bcl-2 as a transgene. Such mice had reduced apoptosis in germinal centers and an excessive number of memory B cells with a low frequency of V gene somatic mutation, including those mutations encoding amino acid exchanges known to enhance affinity. Despite the frequency of AFCs being increased in bcl-2-transgenic mice, the fraction secreting high-affinity antibody in the bone marrow at day 42 remained unchanged compared with controls. The inability of BCL-2 to alter selection of bone marrow AFCs is consistent with these cells being selected within the germinal center on the basis of their affinity being above some threshold rather than their survival being due to a selective competition for an antigen-based signal. Continuous competition for antigen does, however, explain formation of the memory compartment.
Publisher
ROCKEFELLER UNIV PRESS
Keywords
PRIMARY IMMUNE-RESPONSE; AFFINITY MATURATION; SECONDARY RESPONSES; NEGATIVE SELECTION; CYCLE PROGRESSION; CLONAL SELECTION; IN-SITU; ANTIGEN; DEATH; DIFFERENTIATION
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2000-02-07 12:00:00
Last Modified: 0001-01-01 12:00:00
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