Blood, 1 February 2001, Vol. 97, No. 3, pp. 714-719
NEOPLASIA
B-cell development in progressively transformed germinal
centers: similarities and differences compared with classical
germinal centers and lymphocyte-predominant Hodgkin
disease
Andreas Bräuninger,
Wentao Yang,
Hans-Heinrich Wacker,
Klaus Rajewsky,
Ralf Küppers, and
Martin-Leo Hansmann
From the Department of Pathology, University of
Frankfurt, Frankfurt; the Department of Hematopathology, University of
Kiel, Kiel; the Institute for Genetics, University of Cologne, Cologne,
Germany; and the Department of Pathology, Cancer Hospital, Shanghai
Medical University, Shanghai, People's Republic of China.
Progressively transformed germinal centers (PTGCs) are
histologic structures mainly composed of small resting B cells and intermingled proliferating centroblast-like cells. The B-cell differentiation processes within PTGCs and their relation to classical germinal centers (GC) and to lymphocyte-predominant Hodgkin disease (LPHD), with which PTGCs are often associated, are largely unknown. To
address these issues, single small resting (Ki67
)
and proliferating (Ki67+) centroblast-like cells were
isolated from 7 PTGCs of 5 lymph nodes, and rearranged
immunoglobulin genes were amplified and sequenced. Most small resting B
cells were clonally unrelated, and most carried unmutated
immunoglobulin gene rearrangements resembling mantle zone B cells.
Small resting B cells with mutated immunoglobulin gene rearrangements
may represent centrocytes, memory B cells, or both. Among the
centroblast-like Ki67+ cells, expanded B-cell clones were
observed in 6 of 7 PTGCs analyzed. Clonally related V region genes
showed extensive intraclonal diversity, and the mutation pattern
indicated stringent selection of the cells for the expression of
functional antigen receptors. Thus, somatic hypermutation, clonal
expansion, and selection occur also in the disorganized PTGC
microenvironment, as in classical GCs. In lymph nodes affected by
PTGCs, no clonal expansion across the borders of individual PTGCs was
observed, distinguishing PTGCs from LPHD.
