First Author | von Muenchow L | Year | 2017 |
Journal | Eur J Immunol | Volume | 47 |
Issue | 2 | Pages | 394-405 |
PubMed ID | 27925658 | Mgi Jnum | J:249634 |
Mgi Id | MGI:5922321 | Doi | 10.1002/eji.201646638 |
Citation | von Muenchow L, et al. (2017) Pro-B cells propagated in stromal cell-free cultures reconstitute functional B-cell compartments in immunodeficient mice. Eur J Immunol 47(2):394-405 |
abstractText | Up to now long-term in vitro growth of pro-B cells was thought to require stromal cells. However, here we show that fetal liver (FL) and bone marrow (BM) derived pro-B cells can be propagated long-term in stromal cell-free cultures supplemented with IL-7, stem cell factor and FLT3 ligand. Within a week, most cells expressed surface CD19, CD79A, lambda5, and VpreB antigens and had rearranged immunoglobulin D-J heavy chain genes. Both FL and BM pro-B cells reconstituted the B-cell compartments of immuno-incompetent Rag2-deficient mice, with FL pro-B cells generating follicular, marginal zone (MZB) and B1a B cells, and BM pro-B cells giving rise mainly to MZB cells. Reconstituted Rag2-deficient mice generated significant levels of IgM and IgG antibodies to a type II T-independent antigen; mice reconstituted with FL pro-B cells generated surprisingly high IgG1 titers. Finally, we show for the first time that mice reconstituted with mixtures of pro-B and pro-T cells propagated in stromal cell-free in vitro cultures mounted a T-cell-dependent antibody response. This novel stromal cell-free culture system facilitates our understanding of B-cell development and might be applied clinically. |