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.

Annika Katharina Breitfelder

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