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CHaPter 4 Antigen Receptor Genes, Gene Products, and Coreceptors 67

KeY ConCePtS Membrane-Bound Immunoglobulin
B Cell Receptor (BCR) and Coreceptors Igs mediate their effector functions as secreted products of plasma

• The BCR–antigen complex consists of a membrane-bound immuno- cells. However, as membrane-bound structures on mature B cells,
globulin (mIg) that is responsible for antigen recognition and an Igα/β Igs serve as the antigen-recognition component of the BCR
heterodimer that is responsible for transducing the recognition signal complex. Although all Ig classes can be expressed at the cell
into the cell. surface, the vast majority of circulating mature B cells coexpress
• BCR engagement leads to the phosphorylation of tyrosines in the membrane-bound IgM and IgD. Appropriate activation of a naïve
Igα/β immunoreceptor tyrosine-based activation motif (ITAM) motifs. IgM- and IgD-expressing B cell leads to plasma cell differentiation
This signal is then transmitted to one or more other intracellular signaling
pathways. and antibody secretion. The membrane-bound forms of IgM
• Recognition of antigen by B lymphocytes can also involve binding of and IgD are the product of alternative splicing of the Ig transcript
antigen complexed with C3d and IgG to additional B-cell coreceptors. at the 3’, or carboxy terminus, of the heavy chain (Fig. 4.10).
• Binding of complexed antigen by individual coreceptors can lead to The two membrane exons encode the transmembrane hydro-
either positive or negative signals, each of which can influence the phobic stretch of amino acids and an evolutionarily conserved
ultimate outcome of an antigen–B lymphocyte interaction. cytoplasmic tail terminating in lysine, valine, and lysine.
• Deficiency of the components of the BCR antigen complex impairs
B cell development and can lead to agammaglobulinemia.
Signal Transduction and the Ig-α/β
(CD79a/CD79b) Heterodimer
The heterodimeric signal transduction component of the BCR
complex that associates with mIg has been designated CD79. It
B CELL RECEPTOR COMPLEX: STRUCTURE is composed of an Igα (CD79a) and Igβ (CD79b) heterodimer.
AND FUNCTION CD79 is responsible for transporting mIg to the cell surface and
for transducing BCR signals into the cell. 43,44
Although the ability of surface Ig to recognize antigen was CD79a/Igα is encoded by CD79a/MB-1 (chromosome 19q13.2)
appreciated very early, the mechanism by which membrane as a 226 amino acid glycoprotein of approximately 47 kDa. The
immunoglobulin (mIg) transmitted an antigen recognition exact molecular weight depends on the extent of glycosylation.
event to the cell took longer to understand. Specifically, as the CD79b/B29 (chromosome 17q23) encodes CD79b/Igβ, which
predominant isotypes expressed on the surface of mature B is a 229-amino acid glycoprotein of approximately 37 kDa. CD79a
cells, mIgM, and mIgD contain only three amino acid residues and CD79b share an exon–intron structure, which is similar to
exposed to the cytoplasm, it was thought unlikely that these Ig that of the genes that encode the CD3 TCR coreceptor molecules.
heavy chains could function as signal transduction molecules These similarities suggest that both BCR and TCR coreceptors
by themselves. This presumption was eventually proved correct are the progeny of a common ancestral gene. Igα and Igβ both
when it was shown that all membrane Ig isotypes associated contain a single IgSF Ig domain (111 residue C-type for Igα and
noncovalently with a heterodimeric complex consisting of 129 residue V-type for Igβ). Each also contains a highly conserved
two transmembrane proteins, Igα (CD79a) and Igβ (CD79b), transmembrane domain and a 61-(Igα) or 48-(Igβ) amino acid
each of which is capable of transducing signals into the cell cytoplasmic tail that also exhibits striking amino acid evolutionary
(Table 4.3). conservation.
Igα and Igβ are expressed by the earliest committed B-cell
progenitors prior to Igµ H chain rearrangement. The CD79
heterodimer has been observed on the surface of early B-cell
progenitors in the absence of Igµ, although neither protein is
TABLE 4.3 the B-Cell receptor (BCr) and required for progenitors to commit to the B-cell lineage. Later
45
Its Coreceptor Molecules
Molecule M r Chromosome Function
BCr LV Cµ1Cµ2Cµ3Cµ4 pA pA
mIgM (µ 2 L 2 ) 180 000 14 (IgH; 14q.32) Antigen recognition DNA
2 (Igκ; 2p12) S M1 M2
22 (Igλ; 22q11.2)
Ig-α (CD79a) 47 000 19 (19q13.2) Signal transducer Cµ1Cµ2Cµ3Cµ4
Ig-β (CD79b) 37 000 17 (17q23) Signal transducer LV
µsRNA
Coreceptors S
CD21 140 000 1 (1q32) Activating coreceptor
Ligand for C3d, EBV, LV Cµ1Cµ2Cµ3Cµ4 M1 M2
CD23
CD19 95 000 16 (16p11.2) Activating coreceptor µmRNA
Signal transducer
FcγRIIB (CD32) 40 000 1 (1q23-24) Inhibitory coreceptor
Low affinity receptor FIG 4.10 Membrane and Secretory Immunoglobulin M (IgM)
for IgG Are Created by Alternative Splicing. Alternative splicing of
CD22 140 000 19 (19q13.1) Inhibitory coreceptor the Cm carboxy-terminal exons results in messenger RNA (mRNA)
Adhesion molecule transcripts encoding either secreted IgM (µ s RNA) or membrane-
Signal transducer
bound IgM (µ m RNA).