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Immunoglobulin M-degrading enzyme of Streptococcus suis (Ide (Ssuis) ) impairs porcine B cell signaling

Streptococcus suis (S. suis) is an important porcine pathogen, causing severe disease like meningitis and septicemia primarily in piglets. Previous work showed that the IgM-degrading enzyme of S. suis (Ide (Ssuis) ) specifically cleaves soluble porcine IgM and is involved in complement evasion. The...

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Detalles Bibliográficos
Autores principales: Breitfelder, Annika Katharina, Schrödl, Wieland, Rungelrath, Viktoria, Baums, Christoph Georg, Alber, Gottfried, Schütze, Nicole, Müller, Uwe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9980343/
https://www.ncbi.nlm.nih.gov/pubmed/36875121
http://dx.doi.org/10.3389/fimmu.2023.1122808
Descripción
Sumario:Streptococcus suis (S. suis) is an important porcine pathogen, causing severe disease like meningitis and septicemia primarily in piglets. Previous work showed that the IgM-degrading enzyme of S. suis (Ide (Ssuis) ) specifically cleaves soluble porcine IgM and is involved in complement evasion. The objective of this study was to investigate Ide (Ssuis) 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 (Ssuis) _homologue as well as Ide (Ssuis) derived from culture supernatants of S. suis serotype 2 on porcine PBMCs and mandibular lymph node cells. Point-mutated rIde (Ssuis) _homologue_C195S did not cleave the IgM B cell receptor. After receptor cleavage by rIde (Ssuis) _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 (Ssuis) _homologue_C195S. B cell receptor mediated signaling after specific stimulation via the F(ab’)(2) portion was significantly inhibited by rIde (Ssuis) _homologue receptor cleavage in IgM(+) B cells, but not in IgG(+) B cells. Within IgM(+) cells, CD21(+) B2 cells and CD21(-) B1-like cells were equally impaired in their signaling capacity upon rIde (Ssuis) _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 (Ssuis) cleavage efficacy on the IgM B cell receptor and its consequences for B cell signaling.