Studies of Lymphocyte Reconstitution in a Humanized Mouse Model Reveal a Requirement of T Cells for Human B Cell Maturation

  • Lang J
  • Kelly M
  • Freed B
 et al. 
  • 50

    Readers

    Mendeley users who have this article in their library.
  • 35

    Citations

    Citations of this article.

Abstract

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. Of interest, a similar problem has been reported in transplant patients who 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-Rag2(null)Il2rγ(null) 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 T cells are necessary for B cell maturation, as introduction of autologous human T cells expedites the appearance of mature B cells, whereas 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 cell-dependent and T cell-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 validate the use of this animal model to study mechanisms and treatments for the similar delay of functional B cells associated with cord blood transplantations.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • J. Lang

  • M. Kelly

  • B. M. Freed

  • M. D. McCarter

  • R. M. Kedl

  • R. M. Torres

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free