Studies of lymphocyte reconstitution in a humanized mouse model reveal a requirement of T cells for human B cell maturation.

Studies of lymphocyte reconstitution in a humanized mouse model reveal a requirement of T cells for human B cell maturation.
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DOI:
10.4049/jimmunol.1202810
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发表时间:
2013-03-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Pelanda R
Pelanda R
中科院分区:
其他
文献类型:
--
作者:
Lang J;Kelly M;Freed BM;McCarter MD;Kedl RM;Torres RM;Pelanda R

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The hematopoietic humanized mouse (hu-mouse) model is a powerful resource to study and manipulate the human immune system. However, a major and recurrent issue with this model has been the poor maturation of B cells that fail to progress beyond the transitional B cell stage. Interestingly, a similar problem has been reported in transplant patients that receive cord blood stem cells. In this study, we characterize the development of human B and T cells in the lymph nodes (LNs) and spleen of BALB/c-Rag2nullIl2rγnull hu-mice. We find a dominant population of immature B cells in the blood and spleen early, followed by a population of human T cells, coincident with the detection of LNs. Notably, in older mice we observe a major population of mature B cells in LNs and in the spleens of mice with higher T cell frequencies. Moreover, we demonstrate that the T cells are necessary for B cell maturation, as introduction of autologous human T cells expedites the appearance of mature B cells, while in vivo depletion of T cells retards B cell maturation. The presence of the mature B cell population correlates with enhanced IgG and Ag-specific responses to both T-dependent and T-independent challenges, indicating their functionality. These findings enhance our understanding of human B cell development, provide increased details of the reconstitution dynamics of hu-mice, and validates the use of this animal model to study mechanisms and treatments for the similar delay of functional B cells associated with cord blood transplantations.
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