Characterization of human FCRL4-positive B cells

Michel Jourdan (1) , Nicolas Robert (2) , Maïlys Cren (3) , Coraline Thibaut (1) , Christophe Duperray (4) , Alboukadel Kassambara (5, 1) , Michel Cogné (6) , Karin Tarte (7) , Bernard Klein (8, 1, 5) , Jerome Moreaux (1, 5, 8)

1 IGH - Institut de génétique humaine
2 CHU Montpellier
3 Cellules souches normales et cancéreuses
4 Montpellier RIO Imaging - MRI-Cytométrie-IRB [CHU Montpellier]
5 Département d'hématologie biologique[Montpellier]
6 CRIBL - Contrôle de la Réponse Immune B et des Lymphoproliférations
7 MiCa - Microenvironnement et cancer
8 UM1 Médecine - Université Montpellier 1 - UFR de Médecine

FCRL4 is an immunoregulatory receptor that belongs to the Fc receptor-like (FCRL) family. In healthy individuals, FCRL4 is specifically expressed by memory B cells (MBCs) localized in sub-epithelial regions of lymphoid tissues. Expansion of FCRL4+ B cells has been observed in blood and other tissues in various infectious and autoimmune disorders. Currently, the mechanisms involved in pathological FCRL4+ B cell generation are actively studied, but they remain elusive. As in vivo FCRL4+ cells are difficult to access and to isolate, here we developed a culture system to generate in vitro FCRL4+ B cells from purified MBCs upon stimulation with soluble CD40 ligand and/or CpG DNA to mimic T-cell dependent and/or T-cell independent activation, respectively. After 4 days of stimulation, FCRL4+ B cells represented 17% of all generated cells. Transcriptomic and phenotypic analyses of in vitro generated FCRL4+ cells demonstrated that they were closely related to FCRL4+ tonsillar MBCs. They strongly expressed inhibitory receptor genes, as observed in exhausted FCRL4+ MBCs from blood samples of HIV-infected individuals with high viremia. In agreement, cell cycle genes were significantly downregulated and the number of cell divisions was two-fold lower in in vitro generated FCRL4+ than FCRL4- cells. Finally, due to their reduced proliferation and differentiation potential, FCRL4+ cells were less prone to differentiate into plasma cells, differently from FCRL4- cells. Our in vitro model could be of major interest for studying the biology of normal and pathological FCRL4+ cells.

Domains: Life Sciences [q-bio]; Immunology; Life Sciences [q-bio]; Cancer

Michel Jourdan, Nicolas Robert, Maïlys Cren, Coraline Thibaut, Christophe Duperray, et al.. Characterization of human FCRL4-positive B cells. PLoS ONE, 2017, 12 (6), pp.e0179793. ⟨10.1371/journal.pone.0179793⟩. ⟨hal-01560458⟩