Increased expression of CD27 on activated human memory B cells correlates with their commitment to the plasma cell lineage
- Author(s)
- Avery, DT; Ellyard, JI; Mackay, F; Corcoran, LM; Hodgkin, PD; Tangye, SG;
- Details
- Publication Year 2005-04-01,Volume 174,Issue #7,Page 4034-4042
- Journal Title
- JOURNAL OF IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- Plasma cells (PC) or Ig-secreting cells (ISC) are terminally differentiated B cells responsible for the production of protective Ig. ISC can be generated in vitro by culturing human B cells with the T cell-derived stimuli CD40L, IL-2, and IL-10. ISC have traditionally been identified by the increased expression of CD38, analogous to primary human PC, and the acquired ability to secrete Ig. By tracking the proliferation history of activated B cells, we previously reported that the differentiation of memory B cells into CD38(+) B cells is IL- 10 dependent, and increases in frequency with cell division. However, < 50 % of CD38(+) cells secreted Ig, and there was a population of CD38(-) ISC. Thus, the PC phenotype of CD38(+) cells generated in vitro did not correlate with PC function. To address this, we have examined cultures of activated memory B cells to accurately identify the phenotype of ISC generated in vitro. We found that CD27 is also up-regulated on memory B cells in an IL-10-dependent and division-dependent manner, and that ISC segregated into the CD27 high subset of activated memory B cells irrespective of the acquired expression of CD38. The ISC generated in these cultures expressed elevated levels of the transcription factors Blimp-1 and X box-binding protein-1 and reduced levels of Pax-5, and exhibited selective migration toward CXCL12, similar to primary PC. We propose that the differentiation of memory B cells into PC involves a transitional stage characterized by a CD27(high)CD38(-) phenotype with the acquired ability to secrete high levels of Ig.
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Keywords
- IMMUNOGLOBULIN-SECRETING CELLS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; BONE-MARROW; LYMPHOCYTE DIFFERENTIATION; PERIPHERAL-BLOOD; MYELOMA CELLS; BLIMP-1 EXPRESSION; GERMINAL CENTER; CUTTING EDGE; IN-VITRO
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Creation Date: 2005-04-01 12:00:00