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Expanded circulating transitional B cells in a patient with systemic lupus erythematosus

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B-cell development begins in the bone marrow and results in the generation of immature transitional B cells that leave the bone marrow and enter the spleen, where they complete their maturation into mature B cells. Transitional B cells undergo intense selection, resulting in the survival and entry of only a small fraction into the mature B-cell pool. The possibility that abnormalities in transitional B-cell biology might contribute to the development of autoimmunity in systemic lupus erythematosus (SLE) stimulated an examination of the phenotype and immunoglobulin repertoire of transitional B cells in patients with SLE. Initially, we sought to identify human transitional B cells phenotypically, as this had not previously been done in humans. This was facilitated by the identification of an unusual patient with SLE and transient hypogamma-globulinemia. This patient had a very large population of IgD+ CD27- naive B cells, which included an expanded population of what we identified as transitional B cells. These were comparable in phenotype with transitional B cells that we found in normal human bone marrow. These were small, CD19+ CD20hi IgDlo IgMhi CD21- CD23- CD10+ CD24hi CD38hi CD44locells. This population was expanded in this SLE patient and also in children compared with normal adults. Immunoglobulin heavy chain genes were completely unmutated in this population and the repertoire differed significantly from that found in normal adult mature B cells. These results suggest that abnormalities in transitional B-cell biology may contribute to the development of autoantibodies in SLE.

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Keywords

  • Bone Marrow
  • Systemic Lupus Erythematosus
  • Large Population
  • Heavy Chain
  • Systemic Lupus Erythematosus Patient