| First Author | Tian Q | Year | 2006 |
| Journal | J Immunol | Volume | 177 |
| Issue | 4 | Pages | 2412-22 |
| PubMed ID | 16888003 | Mgi Jnum | J:138356 |
| Mgi Id | MGI:3805061 | Citation | Tian Q, et al. (2006) B cells expressing a natural polyreactive autoantibody have a distinct phenotype and are overrepresented in immunoglobulin heavy chain transgenic mice. J Immunol 177(4):2412-22 |
| abstractText | Despite stringent regulation of disease-associated autoantibodies, a substantial proportion of circulating Abs in sera of healthy individuals exhibit self-reactivity. These Abs are referred to as naturally occurring or natural autoantibodies (NAAs). To understand the origin and function of NAAs, we have generated a new site-directed transgenic mouse model in which a prerearranged VDJ gene coding for the H chain of a typical polyreactive NAA, ppc1-5, is inserted into the IgH locus. This H chain, when combined with its original L chain, the lambda1 L chain, yields a NAA that characteristically binds a variety of self and non-self Ags including ssDNA, actin, ubiquitin, and nitrophenyl phosphocholine. Despite their autoreactivity, B cells expressing ppc1-5H/lambda1 NAA are not negatively selected, but rather are overrepresented in the transgenic mice. The shift toward lambda1 expression mainly occurs during the transition of immature to mature B cells in the spleen, suggesting a BCR selection process. The ppc1-5H/lambda1 B cells exhibit a phenotype that is different from those of the known mature B cell populations, and they are located predominantly in the lymphoid follicles of the spleen and the lymph nodes. These B cells are functionally active, producing high levels of Abs in vivo and responding well to BCR stimulation in vitro. The findings indicate that the ppc1-5/lambda1 natural autoantibodies originate from a distinct B cell subset that may be positively selected by virtue of its poly/autoreactivity. |
