Spontaneously Ig-secreting B-1 cells violate the accepted paradigm for expression of differentiation-associated transcription factors.
B-1 cells spontaneously secrete natural Ig that acts as a primary line of defense against infection. A major shortfall in our understanding of this key process centers on the molecular mechanisms regulating natural Ab secretion by B-1 cells. Herein, we demonstrate that secreting B-1 cells use some aspects of the recently recognized plasmacytic differentiation program but deviate from it in important ways. Specifically, we show that key repressors of the plasmacytic program, B cell leukemia/lymphoma-6 and paired box gene 5, are reduced in spontaneously secreting B-1 B cells, as in stimulated differentiated B-2 cells. Surprisingly, we find that key promoters of the plasmacytic program, B lymphocyte inducer of maturation program 1 and X-box binding protein 1, are not up-regulated in secreting B-1 cells, in contrast to secreting B-2 cells. These data demonstrate that B-1 cells operate under a differentiation program that is unique and differs from the paradigm associated with Ig-secreting B-2 cells.
Tumang
Joseph R
JR
Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
Francés
Rubén
R
Yeo
Seung Geun
SG
Rothstein
Thomas L
TL
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D001483:Base Sequence; D002454:Cell Differentiation; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D015870:Gene Expression; D007113:Immunity, Innate; D007136:Immunoglobulins / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009687:Nuclear Proteins / Q000235:genetics; D051757:PAX5 Transcription Factor; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051560:Proto-Oncogene Proteins c-bcl-6; D000071701:Regulatory Factor X Transcription Factors; D012097:Repressor Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D007136:Immunoglobulins; D009687:Nuclear Proteins; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; C513258:Prdm1 protein, mouse; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D000071701:Regulatory Factor X Transcription Factors; D012097:Repressor Proteins; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1