Abstract
Cell migration relies on coordinated activity of chemotactic and guidance receptors. Here, we report a specific role for the RNA-binding protein ZFP36L1 in limiting the abundance of molecules involved in the homing of antibody-secreting cells (ASCs) to the bone marrow (BM). In the absence of ZFP36L1, ASCs build up in the spleen and the liver and show diminished accumulation in the BM. ZFP36L1 facilitates migration by directly regulating G protein-coupled receptor kinase 2 (GRK2) and the integrin chains α4 and β1 in splenic ASCs. Expression of CXCR4 and of the integrins α4 and β1 is differentially regulated on ASCs produced at the early and late stages of the immune response. Consequently, deletion of the Zfp36l1 gene has a stronger effect on BM accumulation of high-affinity ASCs formed late in the response. Thus, ZFP36L1 is an integral part of the regulatory network controlling gene expression during ASC homing.
Highlights
Long-term humoral immunity is derived from the generation and persistence of memory B cells and antibody-secreting cells (ASCs) following infection
It was shown that reduced activation of the integrin β1 on early ASCs in mice deficient for the cochaperone Mzb1 was associated with their impaired trafficking to the bone marrow (BM) (Andreani et al, 2018)
ZFP36L1 in B cells determines the numbers of BM ASCs To identify a role for ZFP36L1 in B cells during humoral immune responses, we used mice with B cell–specific deletion of a conditional Zfp36l1 allele (Zfp36l1fl; Newman et al, 2017)
Summary
Long-term humoral immunity is derived from the generation and persistence of memory B cells and antibody-secreting cells (ASCs) following infection. ASC homing to the BM is guided primarily by the CXCL12/CXCR4 pair (Hauser et al, 2002; Bowman et al, 2002; Luther et al, 2002). It was shown that reduced activation of the integrin β1 on early ASCs in mice deficient for the cochaperone Mzb was associated with their impaired trafficking to the BM (Andreani et al, 2018). While another integrin dimer, α4β7, is mainly thought of as an adhesion molecule directing migration of lymphocytes to the intestine, antibody-blocking and genetic experiments suggest a role for this integrin in BM homing (Katayama et al, 2004; Murakami et al, 2016)
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