Immunoglobulin M-degrading enzyme of Streptococcus suis (IdeSsuis) 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 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 ₕomologueC195S 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 ₕomologueC195S. 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.