title: Porin differentiates TLR mediated proinflammatory response of follicular zone B cell from TLR-unresponsive IL-10 expressing marginal zone B cell.
abstract: TLR-ligands are frequently chosen as candidates for vaccine or adjuvant development because they can primarily bridge innate signaling with adaptive immune responses. Since the adjuvant action of porin, the major outer membrane protein commonly present on Gram-negative bacteria, has been tested on several antigen-presenting cells, we investigated its role in driving systemic immunity which is considered a benchmark for a successful adjuvant. Here, we show porin differentially regulated splenic marginal zone (MZ) and follicular zone (FO) B cell responses in contrast to other classical TLR2-ligands FSL-1 and Pam3CSK4. The protein up-regulated TLR2 and TLR6 and stimulated the activation and costimulatory molecules on FO B cells skewing the cells toward TLR-dependent type-1 cytokine response. However, porin could not up-regulate the TLRs and activate MZ B cells. These cells responded to porin by expressing toll-interacting protein (TOLLIP), the TLR2 and -4 signaling inhibitor along with stimulation of the intracellular pathogen recognition receptor NLR caspase recruitment domain containing protein 5 (NLRC5). The CD1d(hi) MZ B cells released IL-10 unequivocally demonstrating regulatory B cell feature. Immunization with porin also resulted in transient IL-10 expression by the CD19(+)CD21(hi) B cells prior to plasma cell formation. Moreover, the plasma cells developed from the B-2 cell subsets show marked variation in generation of immunoglobulin subclasses. The work delineates multi-faceted role of B cell subsets induced by porin for robust immunity without compromising with the checks and controls.
authors.affiliation: Division of Immunology, National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Debolina
authors.initials: D
authors.lastname: Sinha
authors.affiliation: Division of Immunology, National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Amlan Kanti
authors.initials: AK
authors.lastname: Ghosh
authors.affiliation: Division of Immunology, National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Subhadeep
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Division of Immunology, National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Ratna
authors.initials: R
authors.lastname: Biswas
authors.affiliation: Division of Immunology, National Institute of Cholera and Enteric Diseases, Kolkata, India. Electronic address: shigellaporin@yahoo.com.
authors.forename: Tapas
authors.initials: T
authors.lastname: Biswas
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D004075:Diglycerides / Q000276:immunology; D006090:Gram-Negative Bacteria / Q000737:chemistry*; D007114:Immunization; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D055666:Lipopeptides / Q000276:immunology; D008221:Lymphoid Tissue / Q000033:anatomy & histology / Q000166:cytology / Q000276:immunology*; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000276:immunology; D010950:Plasma Cells / Q000276:immunology; D018272:Porins / Q000276:immunology* / Q000494:pharmacology; D051192:Receptors, Pattern Recognition / Q000276:immunology; D013154:Spleen / Q000033:anatomy & histology / Q000166:cytology / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology*; D051216:Toll-Like Receptor 6 / Q000235:genetics / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D004075:Diglycerides; C460864:FSL-1 lipoprotein, synthetic; C556062:IL10 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D055666:Lipopeptides; C549161:NLRC5 protein, mouse; D009842:Oligopeptides; C508075:Pam(3)CSK(4) peptide; D018272:Porins; D051192:Receptors, Pattern Recognition; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6; C485837:Tollip protein, mouse; D016753:Interleukin-10
keywords: B-2 cell subsets; Cytokines; Immune regulation; Pattern recognition receptors; Porin