PMID- 23335750
OWN - NLM
STAT- MEDLINE
DCOM- 20130405
LR  - 20211021
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 190
IP  - 5
DP  - 2013 Mar 1
TI  - Studies of lymphocyte reconstitution in a humanized mouse model reveal a 
      requirement of T cells for human B cell maturation.
PG  - 2090-101
LID - 10.4049/jimmunol.1202810 [doi]
AB  - 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)Il2rgamma(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.
FAU - Lang, Julie
AU  - Lang J
AD  - Integrated Department of Immunology, National Jewish Health, Denver, CO 80206, 
      USA.
FAU - Kelly, Margot
AU  - Kelly M
FAU - Freed, Brian M
AU  - Freed BM
FAU - McCarter, Martin D
AU  - McCarter MD
FAU - Kedl, Ross M
AU  - Kedl RM
FAU - Torres, Raul M
AU  - Torres RM
FAU - Pelanda, Roberta
AU  - Pelanda R
LA  - eng
GR  - P30 CA046934/CA/NCI NIH HHS/United States
GR  - R21 AI073629/AI/NIAID NIH HHS/United States
GR  - R21 AI105523/AI/NIAID NIH HHS/United States
GR  - R21-AI073629/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20130118
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Immunoglobulin G)
SB  - IM
MH  - Adoptive Transfer
MH  - Age Factors
MH  - Animals
MH  - B-Lymphocytes/*cytology/immunology
MH  - Bone Marrow/immunology
MH  - Cell Communication/immunology
MH  - Cell Differentiation/immunology
MH  - Humans
MH  - Immunoglobulin G/immunology
MH  - Lymph Nodes/*cytology/immunology
MH  - Lymphocyte Count
MH  - Lymphocyte Depletion
MH  - Mice
MH  - Mice, Knockout
MH  - Models, Animal
MH  - Spleen/*cytology/immunology
MH  - T-Lymphocytes/*cytology/immunology/transplantation
PMC - PMC3578183
MID - NIHMS432547
EDAT- 2013/01/22 06:00
MHDA- 2013/04/06 06:00
PMCR- 2014/03/01
CRDT- 2013/01/22 06:00
PHST- 2013/01/22 06:00 [entrez]
PHST- 2013/01/22 06:00 [pubmed]
PHST- 2013/04/06 06:00 [medline]
PHST- 2014/03/01 00:00 [pmc-release]
AID - jimmunol.1202810 [pii]
AID - 10.4049/jimmunol.1202810 [doi]
PST - ppublish
SO  - J Immunol. 2013 Mar 1;190(5):2090-101. doi: 10.4049/jimmunol.1202810. Epub 2013 
      Jan 18.