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

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

doi:10.3389/fimmu.2023.1122808

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

Front Immunol. 2023 Feb 16:14:1122808. doi: 10.3389/fimmu.2023.1122808. eCollection 2023.

Authors

Annika Katharina Breitfelder¹, Wieland Schrödl¹, Viktoria Rungelrath¹, Christoph Georg Baums¹, Gottfried Alber², Nicole Schütze², Uwe Müller²

Affiliations

¹ Institute of Bacteriology and Mycology, Centre for Infectious Diseases, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany.
² Institute of Immunology, Centre for Infectious Diseases, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany.

Abstract

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.

Keywords: B cell receptor; B cell signalling; IdeSsuis; IgM; Streptococcus suis; receptor cleavage.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
B-Lymphocytes
Immunoglobulin M
Receptors, Antigen, B-Cell
Signal Transduction
Streptococcus suis*
Swine

Substances

Receptors, Antigen, B-Cell
Immunoglobulin M

Grants and funding

This work was funded by the German Research Foundation (Deutsche Forschungsgemeinschaft) grants BA 4730/3-2 and AL 371/10-2. The authors acknowledge the support of the University of Leipzig (open access publication fund).