Increased expression of CD27 on activated human memory B cells correlates with their commitment to the plasma cell lineage.
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.
Avery
Danielle T
DT
Centenary Institute of Cancer Medicine and Cell Biology, New South Wales, Australia.
Ellyard
Julia I
JI
Mackay
Fabienne
F
Corcoran
Lynn M
LM
Hodgkin
Philip D
PD
Tangye
Stuart G
SG
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D018929:Cell Culture Techniques; D019070:Cell Lineage; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D006801:Humans; D007136:Immunoglobulins; D007156:Immunologic Memory; D016753:Interleukin-10 / Q000494:pharmacology; D008562:Membrane Glycoproteins; D010950:Plasma Cells / Q000166:cytology* / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis / Q000235:genetics*; D015854:Up-Regulation
D015703:Antigens, CD; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D014157:Transcription Factors; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D016753:Interleukin-10; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1