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Abstract
Most of the knowledge of B cell development has been derived from studies in mice. Although many aspects of human B cell development are similar to those in mice, our current understanding of aspects of human B cell biology is limited. An example of this is transitional B cells. Although transitional B cells are known to exist in humans, detailed characterisation of these cells has not been performed. Human transitional B cells can be identified as CD24++CD38++CD10+ cells and attempts have been made to segregate them into subsets based on the expression level of CD24 and CD38. Here we have identified 2 subsets of human transitional B cells (CD20+CD27-CD10+) based on the differential expression of CD21 (CD21lo and CD21hi). Our data showed that the CD21hi transitional B cell subset has higher expression of the cell surface receptors CD23, CD44, IgD, BAFF-R and of the pro-survival protein Bcl-2 compared to the CD21lo subset. Consistent with these findings, CD21hi transitional B cells exhibited greater in vitro survival and proliferation than CD21lo transitional B cells. Based on the level of self-reactive autoantibodies, CD21lo transitional cell appears to be the less mature and more recent emigrant from the bone marrow (BM) and this correlates with the expression of Lymphoid enhancing binding factor-1 (LEF-1), a transcription factor highly expressed by immature BM B cells. In addition, data from immunodeficient patients as well as those receiving a stem cell transplant demonstrated that the appearance of CD21lo transitional B cells preceded that of CD21hi transitional B cells. We conclude that the CD21lo subset represents the first population of transitional B cells to exit the BM and populate secondary lymphoid tissue.
In addition to this, we have identified a population of CD10+CD27+ B cells that are present in peripheral blood, tonsil and spleen. Expression of CD10 on CD10+CD27+ B cells suggested that this population may be germinal centre (GC) or memory B cells and their presence in the blood may indicate they are a population of circulating GC B cells. However, further analysis revealed that CD10+CD27+ B cells are phenotypically similar to memory and not GC B cells. This was confirmed by upregulation of BCL2 and PRDM1 and downregulation of BCL6. Surface Ig expression revealed that CD10+CD27+ B cells are a subset memory B cells that have undergone Ig class switching. Thus we conclude that CD10+CD27+ B cells represent a subset of IgM- memory B cells.