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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.