| First Author | Krljanac B | Year | 2014 |
| Journal | Eur J Immunol | Volume | 44 |
| Issue | 3 | Pages | 662-72 |
| PubMed ID | 24242887 | Mgi Jnum | J:209090 |
| Mgi Id | MGI:5565652 | Doi | 10.1002/eji.201343484 |
| Citation | Krljanac B, et al. (2014) NF-kappaB2/p100 deficiency impairs immune responses to T-cell-independent type 2 antigens. Eur J Immunol 44(3):662-72 |
| abstractText | Formation of the splenic marginal zone (MZ) depends on the alternative NF-kappaB signaling pathway. Recently, we reported that unrestricted activation of this pathway in NF-kappaB2/p100-deficient (p100(-/-) ) knock-in mice alters the phenotype of MZ stroma and B cells. Here, we show that lack of the p100 inhibitor resulted in an expansion of both MZ B and peritoneal B-1 cells. However, these cells failed to generate proliferating blasts in response to T-cell-independent type 2 (TI-2) Ags, correlating with dampened IgM and absent IgG3 responses. This phenotype was in part due to increased activity of the NF-kappaB subunit RelB. Moreover, p100(-/-) -->B6 BM chimeras were more susceptible to infection by encapsulated Streptococcus pneumoniae bacteria, pathogens that induce TI-2 responses. In contrast to the TI-2 defect, p100 deficiency did not impair immune responses to the TI-1 Ag LPS and p100(-/-) MZ B cells showed normal Ag transportation into B-cell follicles. Furthermore, p100(-/-) MZ B and B-1 cells failed to respond to TI-2 Ags in the presence of WT accessory cells. Thus, NF-kappaB2/p100 deficiency caused a predominant B-cell-intrinsic TI-2 defect that could largely be attributed to impaired proliferation of plasmablasts. Importantly, p100 was also necessary for efficient defense against clinically relevant TI-2 pathogens. |
