Lecture notes
B lymphocytes
- Module
- Introduction (BM108)
- Institution
- The University Of Strathclyde (UOS)
Antibodies b lymphocytes
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# Shorts 5Cell selection and allelic exclusion mediated by the pre-B receptor A rearranged
immunoglobulin heavy chain gene encodes two forms of heavy chain protein, a
membrane form and a secreted form. mRNAs specific for these two forms are
generated as a result of differential splicing and polyadenylation. It is the membrane
form of the immunoglobulin heavy chain that is involved in signal transduction, as
part of the pre-B receptor in pre-B cells, and the antigen receptor in B cells.
The pre-B receptor mediated survival signal is dependent on the presence of the
membrane immunoglobulin heavy chain, surrogate light chains, the Igα/β
heterodimer, Syk and (in man, but not critically so in mice) Btk. This latter kinase is
defective in X-linked agammaglobulinemia, an inherited disease in which the preB to
B cell transition is blocked. Formal evidence suggesting that Src family kinases are
involved in the generation of the pre-B receptor mediated survival signal is lacking,
presumably because of the large number of Src family kinases that can associate
with the pre-B and B cell receptors. However since both Syk and Btk are activated by
Src-family kinases, it is extremely likely that Src family kinases associated with the
pre-B receptor play a role in generating a signal for survival and Figure 1. A
summary of the early satges of B cell development in the bone marrow including the
pre-BCR philatelic exclusion. The pre-B receptor is largely intracellular although it
can be detected with some difficulty on the surface of pre-B cells. No ligand has
been identified for this receptor and it is likely that it signals constitutively, being
triggered by the act of preantigen receptor assembly. It is formally possible that a yet
to be identified ligand exists for the pre-B receptor. However truncated
immunoglobulin heavy chains lacking ligand binding regions can participate in the
generation of pre-B survival and progression signals. Given the fact that pre-antigen
receptors are generated, not to respond (like most receptors) to external clues, but to
monitor if the “right” kind of rearrangement has taken place within a given cell, it is
not unreasonable to suspect that such a receptor does not require an external ligand
for signal initiation. The fully assembled receptor, because of some structural feature
of the surrogate light chains, may be constitutively “on” or may respond to a ligand
made by the pre-B cell itself Clonal deletion and receptor editing during B cell
development in the bone-marrow A proportion of the B cells that are generated each
day express antigen receptors that are directed against selfantigens. B cells bearing
receptors that are cognate for multivalent self-antigens (polysaccharides, membrane
proteins, plasma membrane glycolipids) need to be either eliminated or tolerized in
some other manner. At the immature B cell stage, crosslinking of the B cell receptor
by a multivalent ligand might induce signals that could lead to the induction of
apoptotic death. Such a view has been supported by studies in which “monoclonal
mice” have been generated which express specific immunoglobulin heavy and light
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