title: Studies of lymphocyte reconstitution in a humanized mouse model reveal a requirement of T cells for human B cell maturation.
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.
authors: Integrated Department of Immunology, National Jewish Health, Denver, CO 80206, USA.
authors: Julie
authors: J
authors: Lang
authors: Margot
authors: M
authors: Kelly
authors: Brian M
authors: BM
authors: Freed
authors: Martin D
authors: MD
authors: McCarter
authors: Ross M
authors: RM
authors: Kedl
authors: Raul M
authors: RM
authors: Torres
authors: Roberta
authors: R
authors: Pelanda
mesh_terms: D019264:Adoptive Transfer; D000367:Age Factors; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology* / Q000276:immunology; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D013154:Spleen / Q000166:cytology* / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000637:transplantation
chemical_list: D007074:Immunoglobulin G