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10.1073/pnas.1511270112

http://scihub22266oqcxt.onion/10.1073/pnas.1511270112
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suck abstract from ncbi


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pmid26324941
      Proc+Natl+Acad+Sci+U+S+A 2015 ; 112 (38 ): E5281-9
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  • Complexity of the human memory B-cell compartment is determined by the versatility of clonal diversification in germinal centers #MMPMID26324941
  • Budeus B ; Schweigle de Reynoso S ; Przekopowitz M ; Hoffmann D ; Seifert M ; Küppers R
  • Proc Natl Acad Sci U S A 2015[Sep]; 112 (38 ): E5281-9 PMID26324941 show ga
  • Our knowledge about the clonal composition and intraclonal diversity of the human memory B-cell compartment and the relationship between memory B-cell subsets is still limited, although these are central issues for our understanding of adaptive immunity. We performed a deep sequencing analysis of rearranged immunoglobulin (Ig) heavy chain genes from biological replicates, covering more than 100,000 memory B lymphocytes from two healthy adults. We reveal a highly similar B-cell receptor repertoire among the four main human IgM(+) and IgG(+) memory B-cell subsets. Strikingly, in both donors, 45% of sequences could be assigned to expanded clones, demonstrating that the human memory B-cell compartment is characterized by many, often very large, B-cell clones. Twenty percent of the clones consisted of class switched and IgM(+)(IgD(+)) members, a feature that correlated significantly with clone size. Hence, we provide strong evidence that the vast majority of Ig mutated B cells--including IgM(+)IgD(+)CD27(+) B cells--are post-germinal center (GC) memory B cells. Clone members showed high intraclonal sequence diversity and high intraclonal versatility in Ig class and IgG subclass composition, with particular patterns of memory B-cell clone generation in GC reactions. In conclusion, GC produce amazingly large, complex, and diverse memory B-cell clones, equipping the human immune system with a versatile and highly diverse compartment of IgM(+)(IgD(+)) and class-switched memory B cells.
  • |*Immunologic Memory [MESH]
  • |Adaptive Immunity [MESH]
  • |Adult [MESH]
  • |B-Lymphocytes/*cytology [MESH]
  • |Cell Separation [MESH]
  • |Computational Biology [MESH]
  • |DNA Mutational Analysis [MESH]
  • |Germinal Center/*cytology [MESH]
  • |Humans [MESH]
  • |Immunoglobulin Class Switching [MESH]
  • |Immunoglobulin D/immunology [MESH]
  • |Immunoglobulin Heavy Chains/genetics [MESH]
  • |Immunoglobulin M/immunology [MESH]
  • |Immunoglobulin Variable Region/genetics [MESH]
  • |Male [MESH]
  • |Mutation [MESH]


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