Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 156

somatic mutation of immunoglobulin V regions to generate variants. B cells that
possess high-affinity antigen receptors are selected for survival and proliferation
( affinity maturation ). B-cell receptors are devoted to either BCR signaling or antigen
presentation. Higher-affinity BCRs more effectively capture antigens, which are
subsequently presented to helper T cells, resulting in higher-affinity B cells that can
then receive more T-cell-emitted survival or proliferative signals. Germinal center
B cells with high-affinity B-cell receptors are selectively expanded, as B-cell
receptors promote the selective survival or expansion of higher-affinity germinal
center cells.
Spontaneous and induced signalings are associated with increased phosphatase
activity [ 286 ]. Both SH2 domain-containing phosphatase PTPn6, and SH2 domain-
containing inositol 5-phosphatase are hyperphosphorylated in germinal center cells
and colocalize with liganded B-cell receptors.

3.12.3 Antibodies and B-Cell Receptors

Antibodies are glycoproteins. Their basic functional unit is an immunoglobulin
monomer. Immunoglobulin comprises 4 polypeptidic chains, 2 identical, heavy and
2 identical, light chains connected by disulfide bonds.
Five types of Ig heavy chain exist ( ) that define the class of

antibody (IgA, IgD, IgE, IgG, and IgM). Two types of Ig light chain exist (

α , γ , δ , ,and

).
Secreted antibodies can be monomers (IgD, IgE, and IgG), dimers (IgA), and
pentamers (IgM).
Immunoglobulin monomer is Y shaped. The Y arms contain the antigen-binding
fragment (F AB ) region that is composed of a constant and variable (F V ) domain from
each heavy (V H ) and light (V L ) chain of the antibody. The Y stem corresponds to
the crystallizable fragment (F C ) that can bind to a specific class of Fc receptors as
well as complement components.
Immunoglobulin-M is the first antibody to be produced during an immune
response. It exists as [ 287 ]: (1) a membrane-bound dimer on the surface of B cells,
i.e., the B-cell receptor, and (2) a secreted pentamer ( S IgM), mainly in blood
(occasionally also as a hexamer that lacks a joining [J] chain).
Secreted IgM can be divided into natural (i.e., IgM in foreign antigen-free blood)
and immune types. Immune S IgM type is secreted during exposure to pathogens;
it is antigen specific. Natural S IgM type is produced by B1 and B2 cells. Immune
IgM is mainly produced by B2 cells, but B1a and B1b cells can also secrete IgM in
response to immune signals.
Natural S IgM is characterized by its polyreactivity, as it protects against viral,
bacterial, fungal, and parasitic infections, and enhances pathogen neutralization and
agglutination [ 287 ]. It promotes pathogen clearance in synergy with complement

κ and λ