Memory B lymphocytes migrate to bone marrow in humans

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.

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.