TLR agonists selectively promote terminal plasma cell differentiation of B cell subsets specialized in thymus-independent responses.
Naive murine B cells are known to proliferate and differentiate in response to LPS or CpG, which bind to TLR4 and TLR9, respectively. However, the naive murine B cell compartment is heterogeneous and comprises four different B cell subsets: B-1a, B-1b, marginal zone (MZ), and follicular (FO) B cells. B-1a, B-1b, and MZ B cells are specialized in the response to thymus-independent Ag, and FO B cells are involved in the response to thymus-dependent Ag. This study was undertaken to compare those four naive B cell subsets for their responses to TLR agonists. Quantitative RT-PCR analysis revealed that expression of TLR transcripts differs quantitatively but not qualitatively from one subset to the other. All TLR agonists, with the exception of flagellin and poly(I:C), stimulate B cell proliferation whatever the subset considered. However, TLR ligation leads to massive differentiation of B-1 and MZ B cells into mature plasma cells (PC) but only marginally promotes PC differentiation of FO B cells. Moreover, TLR stimulation strongly up-regulates expression of Blimp-1 and XBP-1(S), two transcription factors known to be instrumental in PC differentiation, in B-1 and MZ B cells but not in FO B cells. Altogether, our findings suggest that B-1 and MZ B cells are poised to PC differentiation in response to the microbial environment and that TLR agonists can be instrumental in stimulating Ab-mediated innate immune protection during microbial infections.
Genestier
Laurent
L
Institut National de la Santé et de la Recherche Médicale Unité 851, IFR128 Biosciences Lyon-Gerland, 21 Avenue Tony Garnier, Lyon, France.
Taillardet
Morgan
M
Mondiere
Paul
P
Gheit
Hanane
H
Bella
Chantal
C
Defrance
Thierry
T
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000378:metabolism; D005408:Flagellin / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000235:genetics*; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D010537:Peritoneum / Q000276:immunology; D010950:Plasma Cells / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D011070:Poly I-C / Q000494:pharmacology; D000074462:Positive Regulatory Domain I-Binding Factor 1; D000071701:Regulatory Factor X Transcription Factors; D012097:Repressor Proteins / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology*; D051193:Toll-Like Receptors / Q000819:agonists* / Q000032:analysis / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation; D000071717:X-Box Binding Protein 1
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C513258:Prdm1 protein, mouse; D000071701:Regulatory Factor X Transcription Factors; D012097:Repressor Proteins; D051193:Toll-Like Receptors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse; D005408:Flagellin; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011070:Poly I-C