- Paper Report
- Open Access
The road to terminal B-cell differentiation
- James B Chung1
© Biomed Central Ltd 2001
- Received: 9 August 2001
- Accepted: 15 August 2001
- Published: 16 August 2001
- B cell development
- plasma cells
- RAG-2 complementation system
- terminal differentiation
- transcription factor
- XBP-1 (X-box-binding protein-1)
Unlike early B cell development and activation, little is known about the factors that lead to the terminal differentiation of mature B lymphocytes to plasma cells. The authors previously found very high levels of X-box-binding protein-1 (XBP-1) transcripts in myeloma cell lines. In this study they sought to analyze the role of XBP-1 in the generation of plasma cells. Analysis is complicated by the fact that XBP-1-deficient mice die in utero, so the work was done using chimeric mice.
The authors found high levels of XBP-1 transcripts in plasma cells of rheumatoid synovium, and in purified B cells committed to plasma cell differentiation. B-cell lines transfected with XBP-1 possessed the surface phenotype of plasma cells. Lymphocytes deficient in XBP-1 failed to produce immunoglobulins in response to activating signals; this was reversed by transducing XBP-1 into the deficient B cells. The XBP-1-/- B cells had the same activation and proliferation profile as control B cells and showed evidence of class switching. Germinal centers formed normally after immunization but there was an absence of plasma cells and a dramatic decrease in immunoglobulin secretion. Interestingly the authors found an increase in the expression of c-Myc, which is usually downregulated as B cells exit the cell cycle. The authors conclude that XBP-1 is specifically required for progression of mature B cells to the plasma B-cell stage.
The RAG-2 complementation system is more fully described in this article:
Chen J, Lansford R, Stewart V, Young F, Alt FW: RAG-2-deficient blastocyst complementation: an assay of gene function in lymphocyte development
Proc Natl Acad Sci USA 1993, 90:4528-4532 (PubMed abstract).