| First Author | Guay HM | Year | 2007 |
| Journal | J Immunol | Volume | 178 |
| Issue | 8 | Pages | 4793-802 |
| PubMed ID | 17404260 | Mgi Jnum | J:145202 |
| Mgi Id | MGI:3833813 | Doi | 10.4049/jimmunol.178.8.4793 |
| Citation | Guay HM, et al. (2007) Spontaneous autoreactive memory B cell formation driven by a high frequency of autoreactive CD4+ T cells. J Immunol 178(8):4793-802 |
| abstractText | Although somatically mutated autoantibodies are characteristic of many autoimmune diseases, the processes that can lead to their development remain poorly understood. We have examined the formation of autoreactive memory B cells in PevHA mice, which express the influenza virus PR8 hemagglutinin (HA) as a transgenic membrane bound neo-self-Ag. Using a virus immunization strategy, we show that PR8 HA-specific memory B cell formation can occur in PevHA mice, even though a major subset of PR8 HA-specific B cells is negatively selected from the primary repertoire. Moreover, PR8 HA-specific memory B cells develop spontaneously in TS1 x PevHA mice, which coexpress a transgenic PR8 HA-specific TCR and contain a high frequency of HA-specific CD4(+) T cells. Notably, autoreactive memory B cell formation occurred in TS1 x PevHA mice even though approximately half of the HA-specific CD4(+) T cells were CD25(+)Foxp3(+) cells that could significantly attenuate, but did not completely abolish HA-specific autoantibody production in an adoptive transfer setting. The findings provide evidence that a high frequency of autoreactive CD4(+) T cells can be sufficient to promote autoreactive memory B cell formation in the absence of signals provided by overt immunization or infection and despite the presence of abundant autoantigen-specific CD4(+)CD25(+)Foxp3(+) regulatory T cells. |
