Journal
IMMUNOLOGY AND CELL BIOLOGY
Volume 99, Issue 8, Pages 865-878Publisher
WILEY
DOI: 10.1111/imcb.12478
Keywords
antibodies; B-cell receptor; B cells; immune tolerance; V(D)J recombination
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Funding
- CHINA Scholarship Council [201603170178]
- NHMRC [1142186]
- NSW Health Early to Mid-Career Fellowship
- National Health and Medical Research Council of Australia [1142186] Funding Source: NHMRC
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The study found that mature naive B cells with lower IgM surface expression in peripheral blood exhibit more diverse IGH features, while B cells with higher surface IgM display more limited IGH repertoire characteristics.
The level of immunoglobulin M (IgM) displayed on the surface of peripheral blood B cells exhibits a broad dynamic range and has been associated with both development and selection. To determine whether IgM surface expression associates with distinct immunoglobulin heavy-chain (IGH) repertoire properties, we performed deep IgM sequencing of peripheral blood transitional and mature naive B cells in the upper and lower quartiles of surface IgM expression for 12 healthy donors. Mature naive B cells within the lowest quartile for surface IgM expression displayed more diverse IGH features including increased complementarity-determining region 3 length, IGHJ6 segment usage and aromatic amino acids compared with mature naive B cells with high surface IgM. There were no differences between IGH repertoires for transitional B cells with high or low surface IgM. These findings suggest that a selection checkpoint during progression of transitional to mature naive B cells reduces the breadth of the IGH repertoire among high surface IgM B cells but that diversity is preserved in B cells expressing low levels of surface IgM.
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