Pro-B cells propagated in stromal cell-free cultures reconstitute functional B-cell compartments in immunodeficient mice

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• 作者：Lilly von Muenchow ; Panagiotis Tsapogas ; Llucia Albertí ; -Servera ; Giuseppina Capoferri ; Marianne Doelz ; Hannie Rolink ; Nabil Bosco ; Rhodri Ceredig and Antonius G. Rolink
• 刊名：European Journal of Immunology
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：47
• 期：2
• 页码：394-405
• 全文大小：2646K
• ISSN：1521-4141

文摘

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, λ5, 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 IgGb>1b> 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.