Checkpoints that control B cell development
#MMPMID25938781
Melchers F
J Clin Invest
2015[Jun]; 125
(6
): 2203-10
PMID25938781
show ga
B cells differentiate from pluripotent hematopoietic stem cells (pHSCs) in a
series of distinct stages. During early embryonic development, pHSCs migrate into
the fetal liver, where they develop and mature to B cells in a transient wave,
which preferentially populates epithelia and lung as well as gut-associated
lymphoid tissues. This is followed by continuous B cell development throughout
life in the bone marrow to immature B cells that migrate to secondary lymphoid
tissues, where they mature. At early stages of development, before B cell
maturation, the gene loci encoding the heavy and light chains of immunoglobulin
that determine the B cell receptor composition undergo stepwise rearrangements of
variable region-encoding gene segments. Throughout life, these gene
rearrangements continuously generate B cell repertoires capable of recognizing a
plethora of self-antigens and non-self-antigens. The microenvironment in which
these B cell repertoires develop provide signaling molecules that play critical
roles in promoting gene rearrangements, proliferation, survival, or apoptosis,
and that help to distinguish self-reactive from non-self-reactive B cells at four
distinct checkpoints. This refinement of the B cell repertoire directly
contributes to immunity, and defects in the process contribute to autoimmune
disease.
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