IL-23 Promotes a Coordinated B Cell Germinal Center Program for Class-Switch Recombination to IgG2b in BXD2 Mice

Abstract

The single-cell RNA sequencing data presented in this article have been submitted to the Gene Expression Omnibus database (https://www.ncbi.nlm.nih.gov/geo/query/ acc.cgi?acc=GSE145922) under accession number GSE145922.

Single Cell Profiling of CD45+ Spinal Cord Cells Reveals Microglial and B Cell Heterogeneity and Crosstalk Following Spinal Cord Injury

“…Indeed, the shift from B cells coalescing in ‘ring-like’ structures at 28 dpi ( Supplemental Figure 3c ) to large foci at 42 dpi suggest these clusters grow from B cells initially invading the spinal cord. The presence of B cells in different stages of maturation and the functional identification of IL-23 mediated signaling lends further support for this possibility, as IL-23 drives germinal center formation 45 . In other tissues, ectopic lymphoid follicles resolve after antigen clearance 63 .…”

“…Uninjured spinal cord B cells were enriched for functions related to DNA and RNA modifications suggestive of antibody refinement such as “regulation of DNA binding,” “regulation of DNA repair,” “regulation of DNA topoisomerase activity,” “positive regulation of isomerase activity,” and “mRNA splicing, via spliceosome.” Subacute SCI-B cells were enriched for multiple pathways regulating neutrophils, including “neutrophil degranulation,” “neutrophil activation involved in immune response,” and “neutrophil mediated immunity;” while chronic SCI-B cells were enriched for “interleukin-23 mediated signaling pathway” and several metabolism pathways. IL-23 signaling coordinates germinal center class-switching and promotes germinal B cell centers 45, 46 . Interestingly, both neutrophils and astrocytic-expression of IL-23 are linked to B cell accumulation and pathology in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis 46 .…”

“…Subacute SCI-B cells were enriched for multiple pathways regulating neutrophils, including "neutrophil degranulation," "neutrophil activation involved in immune response," and "neutrophil mediated immunity;" while chronic SCI-B cells were enriched for "interleukin-23 mediated signaling pathway" and several metabolism pathways. IL-23 signaling coordinates germinal center classswitching and promotes germinal B cell centers 45,46 . Interestingly, both neutrophils and astrocytic-expression of IL-23 are linked to B cell accumulation and pathology in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis 46 .…”

Thymoquinone Modulates Local MMP-9, IL-10, and IgG in Sciatic Nerve Crush Injury Animal Model

“…M1 macrophages generate the cytokines IL-23 that induce autoantibodies. (34,35) The presence of autoantibodies in the deteriorated nerve is indicated by the presence of IgG antibodies in the distal section of the damaged nerve six days after crush injury. (36) This local finding of IgG negatively correlates with neuron regeneration, as elevated local IgG concentrations impair nerve regeneration.…”

Single cell profiling of CD45+ spinal cord cells reveals microglial and B cell heterogeneity and crosstalk following spinal cord injury

“…Subacute SCI-B cells were enriched for multiple pathways regulating neutrophils, including "neutrophil degranulation, " "neutrophil activation involved in immune response, " and "neutrophil mediated immunity, " while chronic SCI-B cells were enriched for "interleukin-23 mediated signaling pathway" and several metabolism pathways. IL-23 signaling coordinates germinal center class-switching and promotes germinal B cell centers [59,60]. Interestingly, both neutrophils and astrocytic-expression of IL-23 are linked to B cell accumulation and pathology in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis [60].…”