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Related Experiment Videos

Memory B lymphocytes migrate to bone marrow in humans

E Paramithiotis1, M D Cooper

  • 1Department of Medicine, Division of Clinical and Developmental Immunology, Howard Hughes Medical Institute, University of Alabama, Birmingham 35294-3300, USA.

Proceedings of the National Academy of Sciences of the United States of America
|January 7, 1997
PubMed
Summary
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Human bone marrow contains mature IgM+ B cells, identified as antigen-experienced lymphocytes. These cells, showing mutations indicative of germinal center selection, suggest a recirculating memory B cell population in the bone marrow.

Area of Science:

  • Immunology
  • Human B cell development

Background:

  • Mature IgM+ B lymphocytes with a specific phenotype (CD10-, CD24lo, IgD+) are acquired postnatally in human bone marrow.
  • These B cells are characterized as large, non-dividing lymphocytes, with some expressing markers of recent activation.

Purpose of the Study:

  • To investigate the origin and characteristics of mature IgM+ B lymphocytes found in human bone marrow.
  • To determine if these B cells have undergone antigen selection and possess features of memory cells.

Main Methods:

  • Analysis of immunoglobulin heavy chain variable region (V(H)) gene transcripts from bone marrow B cells.
  • Sequencing to identify point mutations within the Ig variable region, particularly in complementarity determining regions (CDRs).
  • Assessment of spontaneous and induced immunoglobulin secretion in vitro.

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Main Results:

  • Point mutations were detected in V(H) gene transcripts of mature IgM+ B cells, but not in immature bone marrow B cells.
  • Mutations were concentrated in the CDRs, with a preference for amino acid substitutions, indicating antigen selection in germinal centers.
  • Clonal relatives were identified within individual bone marrow samples, and these cells could be induced to secrete Ig.

Conclusions:

  • The findings suggest that mature IgM+ B cells in human bone marrow are antigen-experienced lymphocytes.
  • The presence of mutations and clonal relationships indicates these cells are derived from germinal center responses.
  • Data support the hypothesis that a subpopulation of memory B lymphocytes generated during antigen responses recirculates to the human bone marrow.