1: Annu Rev Immunol. 2003;21:205-30. Epub 2001 Dec 19. 

Regulatory mechanisms that determine the development and function of plasma
cells.

Calame KL, Lin KI, Tunyaplin C.

Department of Microbiology and Biochemistry, Columbia University College of
Physicians and Surgeons, New York, New York 10032, USA. klc1@columbia.edu

Plasma cells are terminally differentiated final effectors of the humoral immune
response. Plasma cells that result from antigen activation of B-1 and marginal
zone B cells provide the first, rapid response to antigen. Plasma cells that
develop after a germinal center reaction provide higher-affinity antibody and
often survive many months in the bone marrow. Transcription factors Bcl-6 and
Pax5, which are required for germinal center B cells, block plasmacytic
differentiation and repress Blimp-1 and XBP-1, respectively. When
Bcl-6-dependent repression of Blimp-1 is relieved, Blimp-1 ensures that
plasmacytic development is irreversible by repressing BCL-6 and PAX5. In plasma
cells, Blimp-1, XBP-1, IRF4, and other regulators cause cessation of cell cycle,
decrease signaling from the B cell receptor and communication with T cells,
inhibit isotype switching and somatic hypermutation, downregulate CXCR5, and
induce copious immunoglobulin synthesis and secretion. Thus, commitment to
plasmacytic differentiation involves inhibition of activities associated with
earlier B cell developmental stages as well as expression of the plasma cell
phenotype.

Publication Types:
    Review

PMID: 12524387 [PubMed - indexed for MEDLINE]


---------------------------------------------------------------


2: J Virol. 2000 Nov;74(22):10458-67. 

The Epstein-Barr virus promoter initiating B-cell transformation is activated by
RFX proteins and the B-cell-specific activator protein BSAP/Pax5.

Tierney R, Kirby H, Nagra J, Rickinson A, Bell A.

CRC Institute for Cancer Studies, University of Birmingham, Edgbaston,
Birmingham B15 2TT, United Kingdom.

Epstein-Barr virus (EBV)-induced B-cell growth transformation, a central feature
of the virus' strategy for colonizing the human B-cell system, requires full
virus latent gene expression and is initiated by transcription from the viral
promoter Wp. Interestingly, when EBV accesses other cell types, this
growth-transforming program is not activated. The present work focuses on a
region of Wp which in reporter assays confers B-cell-specific activity.
Bandshift studies indicate that this region contains three factor binding sites,
termed sites B, C, and D, in addition to a previously characterized CREB site.
Here we show that site C binds members of the ubiquitously expressed RFX family
of proteins, notably RFX1, RFX3, and the associated factor MIBP1, whereas sites
B and D both bind the B-cell-specific activator protein BSAP/Pax5. In reporter
assays with mutant Wp constructs, the loss of factor binding to any one of these
sites severely impaired promoter activity in B cells, while the wild-type
promoter could be activated in non-B cells by ectopic BSAP expression. We
suggest that Wp regulation by BSAP helps to ensure the B-cell specificity of
EBV's growth-transforming function.

PMID: 11044090 [PubMed - indexed for MEDLINE]


---------------------------------------------------------------