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2015 ; 195
(8
): 3716-24
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A Reassessment of IgM Memory Subsets in Humans
#MMPMID26355154
Bagnara D
; Squillario M
; Kipling D
; Mora T
; Walczak AM
; Da Silva L
; Weller S
; Dunn-Walters DK
; Weill JC
; Reynaud CA
J Immunol
2015[Oct]; 195
(8
): 3716-24
PMID26355154
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From paired blood and spleen samples from three adult donors, we performed
high-throughput VH sequencing of human B cell subsets defined by IgD and CD27
expression: IgD(+)CD27(+) ("marginal zone [MZ]"), IgD(-)CD27(+) ("memory,"
including IgM ["IgM-only"], IgG and IgA) and IgD(-)CD27(-) cells
("double-negative," including IgM, IgG, and IgA). A total of 91,294 unique
sequences clustered in 42,670 clones, revealing major clonal expansions in each
of these subsets. Among these clones, we further analyzed those shared sequences
from different subsets or tissues for VH gene mutation, H-CDR3-length, and VH/JH
usage, comparing these different characteristics with all sequences from their
subset of origin for which these parameters constitute a distinct signature. The
IgM-only repertoire profile differed notably from that of MZ B cells by a higher
mutation frequency and lower VH4 and higher JH6 gene usage. Strikingly, IgM
sequences from clones shared between the MZ and the memory IgG/IgA compartments
showed a mutation and repertoire profile of IgM-only and not of MZ B cells.
Similarly, all IgM clonal relationships (among MZ, IgM-only, and double-negative
compartments) involved sequences with the characteristics of IgM-only B cells.
Finally, clonal relationships between tissues suggested distinct recirculation
characteristics between MZ and switched B cells. The "IgM-only" subset (including
cells with its repertoire signature but higher IgD or lower CD27 expression
levels) thus appear as the only subset showing precursor-product relationships
with CD27(+) switched memory B cells, indicating that they represent germinal
center-derived IgM memory B cells and that IgM memory and MZ B cells constitute
two distinct entities.
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