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Flexible ordering of antibody class switch and V(D)J joining during B-cell ontogeny.
[omenn syndrome]
V
(
D
)
J
joining
is
mediated
by
RAG
recombinase
during
early
B-
lymphocyte
development
in
the
bone
marrow
(
BM
)
.
Activation-induced
deaminase
initiates
isotype
switching
in
mature
B
cells
of
secondary
lymphoid
structures
.
Previous
studies
questioned
the
strict
ontological
partitioning
of
these
processes
.
We
show
that
pro-
B
cells
undergo
robust
switching
to
a
subset
of
immunoglobulin
H
(
IgH
)
isotypes
.
Chromatin
studies
reveal
that
in
pro-
B
cells
,
the
spatial
organization
of
the
Igh
locus
may
restrict
switching
to
this
subset
of
isotypes
.
We
demonstrate
that
in
the
BM
,
V
(
D
)
J
joining
and
switching
are
interchangeably
inducible
,
providing
an
explanation
for
the
hyper-
IgE
phenotype
of
Omenn
syndrome
.