title: Toll-like receptor agonists synergize with CD40L to induce either proliferation or plasma cell differentiation of mouse B cells.
abstract: In a classical dogma, pathogens are sensed (via recognition of Pathogen Associated Molecular Patterns (PAMPs)) by innate immune cells that in turn activate adaptive immune cells. However, recent data showed that TLRs (Toll Like Receptors), the most characterized class of Pattern Recognition Receptors, are also expressed by adaptive immune B cells. B cells play an important role in protective immunity essentially by differentiating into antibody-secreting cells (ASC). This differentiation requires at least two signals: the recognition of an antigen by the B cell specific receptor (BCR) and a T cell co-stimulatory signal provided mainly by CD154/CD40L acting on CD40. In order to better understand interactions of innate and adaptive B cell stimulatory signals, we evaluated the outcome of combinations of TLRs, BCR and/or CD40 stimulation. For this purpose, mouse spleen B cells were activated with synthetic TLR agonists, recombinant mouse CD40L and agonist anti-BCR antibodies. As expected, TLR agonists induced mouse B cell proliferation and activation or differentiation into ASC. Interestingly, addition of CD40 signal to TLR agonists stimulated either B cell proliferation and activation (TLR3, TLR4, and TLR9) or differentiation into ASC (TLR1/2, TLR2/6, TLR4 and TLR7). Addition of a BCR signal to CD40L and either TLR3 or TLR9 agonists did not induce differentiation into ASC, which could be interpreted as an entrance into the memory pathway. In conclusion, our results suggest that PAMPs synergize with signals from adaptive immunity to regulate B lymphocyte fate during humoral immune response.
authors: CNRS UPR 9021, Immunologie et Chimie Thérapeutiques, Institut de Biologie Moléculaire et Cellulaire, 67084, Strasbourg, France.
authors: Emmanuelle
authors: E
authors: Boeglin
authors: Cristian R
authors: CR
authors: Smulski
authors: Susana
authors: S
authors: Brun
authors: Sara
authors: S
authors: Milosevic
authors: Pascal
authors: P
authors: Schneider
authors: Sylvie
authors: S
authors: Fournel
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D023201:CD40 Ligand / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003564:Cytidine Deaminase / Q000378:metabolism; D005786:Gene Expression Regulation; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D010950:Plasma Cells / Q000166:cytology* / Q000276:immunology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D051193:Toll-Like Receptors / Q000819:agonists* / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: C513258:Prdm1 protein, mouse; D012333:RNA, Messenger; D051193:Toll-Like Receptors; D014157:Transcription Factors; D023201:CD40 Ligand; D000074462:Positive Regulatory Domain I-Binding Factor 1; D017493:Leukocyte Common Antigens; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase