Post-Transplantation B Cell Function in Different Molecular Types of SCID

被引:51
作者
Buckley, Rebecca H. [1 ,2 ]
Win, Chan M. [3 ]
Moser, Barry K. [4 ]
Parrott, Roberta E. [1 ]
Sajaroff, Elisa [1 ]
Sarzotti-Kelsoe, Marcella [2 ,3 ]
机构
[1] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA
[2] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA
[3] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA
[4] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA
基金
美国国家卫生研究院;
关键词
B cell function; B cell chimerism; bone marrow transplantation; severe combined immunodeficiency; molecular type; memory B cells; SEVERE COMBINED IMMUNODEFICIENCY; BONE-MARROW-TRANSPLANTATION; STEM-CELL; IMMUNE RECONSTITUTION; SINGLE-CENTER; SERUM IMMUNOGLOBULINS; THYMIC OUTPUT; GENE-THERAPY; DEFICIENCY; ENGRAFTMENT;
D O I
10.1007/s10875-012-9797-6
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Purpose Severe combined immunodeficiency (SCID) is a syndrome of diverse genetic cause characterized by profound deficiencies of T, B and sometimes NK cell function. Non-ablative HLA-identical or rigorously T cell-depleted haploidentical parental bone marrow transplantation (BMT) results in thymus-dependent genetically donor T cell development in the recipients, leading to a high rate of long-term survival. However, the development of B cell function has been more problematic. We report here results of analyses of B cell function in 125 SCID recipients prior to and long-term after non-ablative BMT, according to their molecular type. Methods Studies included blood immunoglobulin measurements; antibody titers to standard vaccines, blood group antigens and bacteriophage Phi X 174; flow cytometry to examine for markers of immaturity, memory, switched memory B cells and BAFF receptor expression; B cell chimerism; B cell spectratyping; and B cell proliferation. Results The results showed that B cell chimerism was not required for normal B cell function in IL7R alpha-Def, ADA-Def and CD3-Def SCIDs. In X-linked-SCID, Jak3-Def SCID and those with V-D-J recombination defects, donor B cell chimerism was necessary for B cell function to develop. Conclusion The most important factor determining whether B cell function develops in SCID T cell chimeras is the underlying molecular defect. In some types, host B cells function normally. In those molecular types where host B cell function did not develop, donor B cell chimerism was necessary to achieve B cell function. 236 words
引用
收藏
页码:96 / 110
页数:15
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