Original Research ARTICLE
TLR9 SIGNALING SUPPRESSES THE CANONICAL PLASMA CELL DIFFERENTIATION PROGRAM IN FOLLICULAR B CELLS.
- 1Immunology, Universidade Federal do Rio de Janeiro, Brazil
- 2Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil
- 3Instituto Gulbenkian de Ciência (IGC), Portugal
The relative potency and quality of mouse B cell response to Toll-like receptors (TLRs) signaling varies significantly depending on the B cell subset and on the TLR member being engaged. Although it has been shown that marginal zone cells respond faster than follicular (FO) splenic B cells to TLR4 stimulus, FO B cells retain full capacity to proliferate and generate plasmablasts and plasma cells (PBs/PCs) with 2-3 days delayed kinetics. It is not clear whether this scenario could be extended to other members of the TLR family. Here, using quantitative cell culture conditions optimized for B cell growth and differentiation, we show that TLR9 signaling by CpG, while promoting vigorous proliferation, completely fails to induce differentiation of FO B cells into PBs/PCs. Little or absent Ig secretion following TLR9 stimulus was accompanied by lack of expression of cell surface markers and canonical transcription factors involved in PB/PC differentiation. Moreover, not only TLR9 did not induce plasmocyte differentiation, but it also strongly inhibited the massive PB/PC differentiation of FO B cells triggered by LPS/TLR4. Our study reveals unexpected opposite roles for TLR4 and TLR9 in the control of plasma cell differentiation program and disagrees with previous conclusions obtained in high-density cultures conditions on the generation of plasmocytes by TRL9 signaling. The potential implications of these findings on the role of TLR9 in controlling self tolerance, clonal sizes and regulation of humoral responses are discussed.
Keywords: follicular B cell, Plasma cell, TLR9, TLR4, Limiting dilution
Received: 29 Mar 2018;
Accepted: 13 Sep 2018.
Edited by:Ana María Hernández, Center of Molecular Immunology (Cuba), Cuba
Reviewed by:Hassan Abolhassani, Tehran University of Medical Sciences, Iran
Elissa Deenick, Garvan Institute of Medical Research, Australia
Copyright: © 2018 Baptista, Granato, Canto, Ferreira, Vale, Coutinho, Bellio and Nobrega. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Prof. Alberto Nobrega, Universidade Federal do Rio de Janeiro, Immunology, av Carlos Chagas Filho 373, Centro de Ciencias de Saude bloco D sala D-35, Rio de Janeiro, 21941-902, RJ, Brazil, email@example.com