in vivo

Laboratory for
Immunological Memory
The traditional view supports the concept
that high-affinity B cell variants generated
in the germinal centers (GCs) differentiate into
long-lasting antibody-forming cells and memory
B cells. This scenario is based primarily on
the observation of affinity maturation and the
accumulation of a large number of somatic
mutations in antigen-specific hybridoma cell
lines established from the secondary response.
Furthermore, a rapid reduction in the number of
Ig + GC B cells during the second week of the
response coincided with the appearance of
memory phenotype B cells, leading to the idea
that GC B cells convert to memory B cells late
in the immune response. In contrast, we have
previously suggested that at least some of
the memory B cells are generated during the
early immune response, probably prior to the
development of germinal centers. However,
the population dynamics during memory B cell
development remain largely unknown, making
the experimental resolution of this important
issue difficult.
Establishment of memory lineage
precursors during the early phase of the
immune response
Group director
Toshitada Takemori
Researcher
Guest Researcher
: Tomohiro Kaji
: Yoshimasa Takahashi
Technical Assistant : Akiko Sugimoto
Junko Taka
Assistant
: Tomoko Takahashi
To address this question, we have used
a 6-color FACS system to analyze the origin,
selection, function and gene expression profiles
in memory B cells at different time points after
immunization. We observed that, in contrast to
the traditional view, antigen-specific memory
precursors were identified in the spleen
concurrently with GC lineage cells from day 5 to
day 6 after immunization, accompanying efficient
proliferation and isotype-class switch from IgM
to IgG1 . Memory precursors are subsequently
recruited into the IgG1 + memory compartment
and sustained for a long period, although these
cells appear to attain full functional development
as the immune response progresses. Cluster
analysis for all microarrays demonstrate that
memory B cell pools at different time points
after immunization are a population independent
from GC B cell and plasma cell populations and
naïve B cells. NP-specific IgG1 + memory B cells
established a unique VH gene repertoire during
the early immune response, a repertoire distinct
from that of GC B cells, raising the question of
whether GC B cell progeny are in fact recruited
into the memory compartment. We concluded
from these results that memory precursor cells
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