| First Author | Carey JB | Year | 2008 |
| Journal | J Exp Med | Volume | 205 |
| Issue | 9 | Pages | 2043-52 |
| PubMed ID | 18710933 | Mgi Jnum | J:138974 |
| Mgi Id | MGI:3806924 | Doi | 10.1084/jem.20080559 |
| Citation | Carey JB, et al. (2008) Repertoire-based selection into the marginal zone compartment during B cell development. J Exp Med 205(9):2043-52 |
| abstractText | Marginal zone (MZ) B cells resemble fetally derived B1 B cells in their innate-like rapid responses to bacterial pathogens, but the basis for this is unknown. We report that the MZ is enriched in 'fetal-type' B cell receptors lacking N regions (N(-)). Mixed bone marrow (BM) chimeras, made with adult terminal deoxynucleotidyl transferase (TdT)(+/+) and TdT(-/-) donor cells, demonstrate preferential repertoire-based selection of N(-) B cells into the MZ. Reconstitution of irradiated mice with adult TdT(+/+) BM reveals that the MZ can replenish N(-) B cells in adult life via repertoire-based selection and suggest the possibility of a TdT-deficient precursor population in the adult BM. The mixed chimera data also suggest repertoire-based bifurcations into distinct BM and splenic maturation pathways, with mature 'recirculating' BM B cells showing a very strong preference for N(+) complementarity-determining region (CDR) 3 compared with follicular B cells. Because the T1 and MZ compartments are both the most enriched for N(-) H-CDR3, we propose a novel direct T1-->MZ pathway and identify a potential T1-MZ precursor intermediate. We demonstrate progressive but discontinuous repertoire-based selection throughout B cell development supporting multiple branchpoints and pathways in B cell development. Multiple differentiation routes leading to MZ development may contribute to the reported functional heterogeneity of the MZ compartment. |
