Skip to Main content Skip to Navigation

Efficient Plasma Cell Differentiation and Trafficking Require Cxcr4 Desensitization

Abstract : CXCR4 plays a central role in B cell immune response, notably by promoting plasma cell (PC) migration and maintenance in the bone marrow (BM). Gain-of-function mutations in CXCR4 affecting receptor desensitization have been reported in the rare immunodeficiency called WHIM syndrome (WS). Despite lymphopenia, patients mount an immune response but fail to maintain it over time. Using a knockin mouse model phenocopying WS, we showed that, counter-intuitively, a gain of Cxcr4 function inhibited the maintenance of antibody titers after immunization. Although the Cxcr4 mutation intrinsically and locally promoted germinal center response and PC differentiation, antigen-specific PCs were barely detected in the BM, a defect mirrored by early accumulation of immature plasmablasts potentially occupying the survival niches for long-lived PCs. Therefore, fine-tuning of Cxcr4 desensitization is critically required for efficient PC differentiation and maintenance, and absence of such a regulatory process may account for the defective humoral immunity observed in WS patients.
Document type :
Journal articles
Complete list of metadatas

Cited literature [47 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-02439879
Contributor : Nicolas Fazilleau <>
Submitted on : Tuesday, January 14, 2020 - 6:23:35 PM
Last modification on : Tuesday, February 18, 2020 - 3:32:02 PM

File

1-s2.0-S2211124716311640-main....
Publication funded by an institution

Identifiers

Citation

Vincent Biajoux, Jessica Natt, Christelle Freitas, Nagham Alouche, Antoine Sacquin, et al.. Efficient Plasma Cell Differentiation and Trafficking Require Cxcr4 Desensitization. Cell Reports , Elsevier Inc, 2016, 17 (1), pp.193-205. ⟨10.1016/j.celrep.2016.08.068⟩. ⟨inserm-02439879⟩

Share

Metrics

Record views

27

Files downloads

38