Biomedical Engineering Reference
In-Depth Information
the B cell receptor, which is a membrane-bound form of antibody.
During the maturation of B cell, the gene encoding the B cell receptor
is rearranged and mutated in a random fashion, which leads to
expression of a receptor with a unique ligand, i.e., antigen, recognizing
potential. It is estimated that the resulting repertoire of unique B cell
receptors are in the order of 10
11
, which is further expanded during
B cell division by a high frequency of mutations in the antigen-
recognizing part of the receptor [1]. This explains the astonishing
ability of the immune system to produce antibodies to nearly any
antigen introduced in the body. Before secreted antibody to protein
antigens is produced, B cell maturation is required, which involves
another subset of human immune cells, the T cells. The T cell is an
important, albeit not the only, source of soluble factors (“cytokines”)
that regulate the function of B cells and other leukocytes.
There are four types of secreted antibodies, namely the IgA,
IgG, IgM, and IgE isotypes. All immunoglobulins are built from a
common structural unit consisting of two covalently linked heavy
chains with three or four constant domains (C
H
) and one domain
containing the variable antigen recognition site (V
H
). The heavy
chains are covalently linked with two light chains each with one
constant (C
L
) and variable domain (V
L
). IgG and IgE are monomers
of this subunit with three and four C
H
domains, respectively. In
blood, IgA is monomeric. On mucosal surfaces in gastrointestinal
tract, IgA is the dominant immunoglobulin and forms a dimeric
complex also containing the J chain, which links IgA molecules, and a
proteolytic fragment of the poly Ig receptor designated the secretory
component. IgM is the largest molecule among the isotypes with a
cross-sectional diameter of approximately 35 nm [4]. Secreted IgM
consists of a planar pentamer of the structural unit together with
the J chain or as a hexamer of the structural unit without the J chain
(Figure. 10.1).
Following the initial recognition of an antigen a B cell produces
mainly IgM antibody. Further B cell stimulation in the lymph node
may change the isotype of the secreted antibody (“class switching”)
to either IgA, IgG, or IgE, all with the same antigen specificity as the
initially produced IgM. There is conflicting data concerning the role
of T cells in this process, probably due to that the cytokines required
for class switching may be produced by other cells than T cells [5, 6].
This is important since it implies that class-switching also occurs for
antibodies directed to T-cell independent antigens, i.e., antibodies
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