Immunoglobulin class switching appears to be regulated by B-cell antigen receptor-specific T-cell action.
Immunoglobulin class switching appears to be regulated by B-cell antigen receptor-specific T-cell action.
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DOI：
10.1002/eji.201141857
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发表时间：
2012-04
影响因子：
5.4
通讯作者：
Lemke, Hilmar
中科院分区：
文献类型：
--
作者：
Lange, Hans;Hecht, Oliver;Zemlin, Michael;Trad, Ahmad;Tanasa, Radu I.;Schroeder, Harry W., Jr.;Lemke, Hilmar
关键词：
抗原亲和力通常被认为是在T细胞依赖的类开关重组（CSR）和免疫成熟过程中发生的显性克隆型选择背后的驱动力。为了验证这一观点，我们分析了针对半抗原2-苯基氯唑酮（phOx）的天然单克隆抗体的可变基因库，以及phOx蛋白载体诱导的胸腺依赖性或ficoll诱导的胸腺非依赖性抗原刺激后产生的单克隆抗体。与预期相反，IgM异质性的程度被证明是相似的，来自这三个群体的许多IgM表现出与经典的Ox1克隆型相似甚至更大的亲和力，Ox1克隆型在主要和记忆IgG中仅在CSR后占主导地位。在CSR期间选择的克隆群体显示出减少的VH/VL库，丰富了更短且更均匀的CDR-H3长度的可变结构域，并且几乎完全剥夺了由大型VH1家族编码的可变结构域。因此，与目前的模式相反，在CSR过程中，t细胞依赖性克隆选择似乎选择了VH家族和CDR-H3环含量，即使替代克隆提供的亲和力与对抗原的亲和力相似。
Antigen affinity is commonly viewed as the driving force behind the selection for dominant clonotypes that can occur during the T cell-dependent processes of class switch recombination (CSR) and immune maturation. To test this view, we analyzed the variable gene repertoires of natural monoclonal antibodies to the hapten 2-phenyloxazolone (phOx) as well as those generated after phOx protein carrier-induced thymus-dependent or Ficoll-induced thymus independent antigen stimulation. In contrast to expectations, the extent of IgM heterogeneity proved similar and many IgM from these three populations exhibited similar or even greater affinities than the classic Ox1 clonotype that dominates only after CSR among primary and memory IgG. The population of clones that were selected during CSR exhibited a reduced VH/VL repertoire that was enriched for variable domains with shorter and more uniform CDR-H3 lengths and almost completely stripped of variable domains encoded by the large VH1 family. Thus, contrary to the current paradigm, T-cell dependent clonal selection during CSR appeared to select for VH family and CDR-H3 loop content even when the affinity provided by alternative clones exhibited similar to increased affinity for antigen.
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DOI：
10.1084/jem.20092712
发表时间：
2010-09-27
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Guo W;Smith D;Aviszus K;Detanico T;Heiser RA;Wysocki LJ
通讯作者：
Wysocki LJ
影响因子：
64.8
作者：
FOOTE, J;MILSTEIN, C
通讯作者：
MILSTEIN, C
影响因子：
5.8
作者：
Gatto, Dominique;Bauer, Monika;Bachmann, Martin F.
通讯作者：
Bachmann, Martin F.
影响因子：
2.8
作者：
AUSTRUP, F;KODELJA, V;KOLSCH, E
通讯作者：
KOLSCH, E
DOI：
10.1007/s00281-004-0182-2
发表时间：
2005-03-01
期刊：
SPRINGER SEMINARS IN IMMUNOPATHOLOGY
影响因子：
--
作者：
Baumgarth, N;Tung, JW;Herzenberg, LA
通讯作者：
Herzenberg, LA