AUTHOR=Breitfelder Annika Katharina , Schrödl Wieland , Rungelrath Viktoria , Baums Christoph Georg , Alber Gottfried , Schütze Nicole , Müller Uwe 

TITLE=Immunoglobulin M-degrading enzyme of Streptococcus suis (IdeSsuis) impairs porcine B cell signaling

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1122808

DOI=10.3389/fimmu.2023.1122808

ISSN=1664-3224

ABSTRACT=<p><italic>Streptococcus suis</italic> (<italic>S. suis</italic>) is an important porcine pathogen, causing severe disease like meningitis and septicemia primarily in piglets. Previous work showed that the IgM-degrading enzyme of <italic>S. suis</italic> (Ide<italic><sub>Ssuis</sub></italic>) specifically cleaves soluble porcine IgM and is involved in complement evasion. The objective of this study was to investigate Ide<italic><sub>Ssuis</sub></italic> cleavage of the IgM B cell receptor and subsequent changes in B cell receptor mediated signaling. Flow cytometry analysis revealed cleavage of the IgM B cell receptor by recombinant (r) Ide<italic><sub>Ssuis</sub></italic>_homologue as well as Ide<italic><sub>Ssuis</sub></italic> derived from culture supernatants of <italic>S. suis</italic> serotype 2 on porcine PBMCs and mandibular lymph node cells. Point-mutated rIde<italic><sub>Ssuis</sub></italic>_homologue_C195S did not cleave the IgM B cell receptor. After receptor cleavage by rIde<italic><sub>Ssuis</sub></italic>_homologue, it took at least 20 h for mandibular lymph node cells to restore the IgM B cell receptor to levels comparable to cells previously treated with rIde<italic><sub>Ssuis</sub></italic>_homologue_C195S. B cell receptor mediated signaling after specific stimulation <italic>via</italic> the F(ab’)<sub>2</sub> portion was significantly inhibited by rIde<italic><sub>Ssuis</sub></italic>_homologue receptor cleavage in IgM<sup>+</sup> B cells, but not in IgG<sup>+</sup> B cells. Within IgM<sup>+</sup> cells, CD21<sup>+</sup> B2 cells and CD21<sup>-</sup> B1-like cells were equally impaired in their signaling capacity upon rIde<italic><sub>Ssuis</sub></italic>_homologue B cell receptor cleavage. In comparison, intracellular B cell receptor independent stimulation with tyrosine phosphatase inhibitor pervanadate increased signaling in all investigated B cell types. In conclusion, this study demonstrates Ide<italic><sub>Ssuis</sub></italic> cleavage efficacy on the IgM B cell receptor and its consequences for B cell signaling.</p>