4.7 Article

Intrinsic constraint on plasmablast growth and extrinsic limits of plasma cell survival

Journal

JOURNAL OF EXPERIMENTAL MEDICINE
Volume 192, Issue 6, Pages 813-821

Publisher

ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.192.6.813

Keywords

plasma cell survival; plasmablast growth; hypermutation; immunoglobulin class switch; spleen

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B cells recruited into splenic antibody responses grow exponentially, either in extrafollicular foci as plasmablasts, or in follicles where they form germinal centers. Both responses yield plasma cells. Although many splenic plasma cells survive <3 d, some live much longer. This study shows that ea;ly plasma cell death relates to a finite capacity of the spleen to sustain plasma cells rather than a life span endowed by the cell's origin or the quality of antibody it produces. Antibody responses were compared where the peak numbers of plasma cells in spleen sections varied between 100 and 5,000 cells/mm(2). In each response, plasmablast clones divided some five times, with the peak numbers of plasma cells produced relating directly to the number of B cells recruited into the response. The spleen seems to have the capacity to sustain between 20 and 100 plasma cells/mm(2). When mis number is exceeded, there is a loss of excess cells. Immune globulin variable region gene sequencing, and 5-bromo-2'-deoxyuridine pulse-chase studies indicate that long-lived splenic plasma cells are a mixture of cells derived from the extrafollicular and germinal center responses and cells derived from virgin and memory B cells. Only a proportion has switched immunoglobulin class.

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