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Blood, Vol. 93 No. 1 (January 1), 1999:
pp. 226-234
Marginal-Zone B Cells in the Human Lymph Node and Spleen Show Somatic
Hypermutations and Display Clonal Expansion
Anne Tierens,
Jan Delabie,
Lieve Michiels,
Peter Vandenberghe, and
Chris De Wolf-Peeters
From the Departments of Pathology and Hematology, University
Hospitals of Leuven; and the Experimental Genetics Group, Flemish
Institute for Biotechnology, Center for Human Genetics, University of
Leuven, Leuven, Belgium.
Splenic marginal-zone B cells, marginal-zone B cells of Peyer's
patches in the gut, and nodal marginal-zone B cells (also identified as
monocytoid B cells) share a similar morphology and immunophenotype.
These cells likely represent a distinct subset of B cells in humans and
rodents, but their precise ontogenetic relationship as well as their
origin from B cells of the germinal center is still debated. To study
this, we performed a mutation analysis of the rearranged immunoglobulin
variable genes (VH) of microdissected single nodal and
splenic marginal-zone cells. In addition, we investigated the presence
of proliferating cells and B-cell clones in the human splenic and nodal
marginal zone as well as adjacent germinal centers. This was performed
by immunohistochemical staining for the Ki-67 antigen and denaturing
gradient gel analysis of amplified immunoglobulin heavy chain genes'
complementarity determining region 3 of microdissected cell clusters. A
variable subset of nodal and splenic marginal-zone B cells showed
somatic mutations in their rearranged VH genes, indicating
that both virgin and memory B cells are present in the nodal and
splenic marginal zone. Nodal and splenic marginal-zone B cells
preferentially rearranged VH3 family genes such as DP47,
DP49, DP54, and DP58. A preferential rearrangement of the same
VH genes has been shown by others in the peripheral
CD5 IgM+ B cells. These data
suggest that the splenic and nodal marginal-zone B cells are closely
related B-cell subsets. We also showed that marginal-zone B cells may
cycle and that clones of B cells are frequently detected in the nodal
as well as the splenic marginal zone. These clones are not related to
those present in adjacent germinal centers. These data favor the
hypothesis that clonal expansion occurs in the marginal zone. Whether
the somatic hypermutation mechanism is activated during the clonal
expansion in the marginal zone and which type of immune response
triggers the clonal expansion need to be elucidated.
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Related Letter in Blood Online:
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Monocytoid B cells
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Blood 2000 96: 1612-1614.
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