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INTRODUCTION

This section focuses on the principal molecular biologic methods that have been developed to study cutaneous lymphoid infiltrates. It is presented as a review divided into 5 parts: antigen receptor genes, polymerase chain reaction–based assays, molecular biologic findings, clinical applications, and conclusions.

ANTIGEN RECEPTOR GENES

Immunoglobulin (Ig) molecules are the antigen-specific receptor of B cells. Each Ig molecule is a protein heterodimer consisting of 2 heavy chains and 2 light chains linked by disulfide bridges. Each B cell expresses a unique Ig molecule containing only 1 of 2 possible types of Ig light chains (Kappa or Lambda); thus the clonal progeny of a B cell would result in a B-cell population with the same Ig molecule and is Ig light chain restricted—that is, either κ or λ (Fig. A3-1A). T-cell receptors (TCRs) are present on T cells and are glycoproteins composed of two possible combinations of heterodimers usually linked by disulfide bridges in association with the CD3 complex.1-3 Four different protein chains of the human TCR are involved in antigen binding: α, β, γ, and δ. The TCR is expressed on the cell surface of T lymphocytes as an αβ or γδ heterodimer and is responsible for antigen recognition (Fig. A3-1B). The vast majority of circulating mature T cells express αβ TCR while γδ T cells are a minor subset and are mostly found in the GI tract, skin, spleen, and other extranodal sites.4 Similar to B cells, each T cell bears a unique TCR and a clonal T-cell proliferation would possess the same TCR.

FIGURE A3-1

(A) Immunoglobulin receptors consist of heavy chain and light chain. The variable region includes the antigen binding site and undergoes somatic hypermutation during B-cell maturation (affinity maturation). The light chains are either kappa or lambda subtypes. (B) T-cell receptors are either αβ or γδ subtypes. The antigen binding sites are part of the variable region. Each B and T cell bears a unique immunoglobulin or T-cell receptor, respectively; thus clonal progeny of a neoplastic lymphocyte would also show the same receptor gene rearrangement, which can be measured by PCR or Southern blot assays. Additionally, in case of neoplastic B-cell population, the progeny would demonstrate the same light chain subtype. (Printed with permission from © Mount Sinai Health System.)

Each Ig and TCR protein chain consists of 3 to 4 distinct regions encoded by gene segments called variable (V), diversity (D), joining (J), and constant (C). Whereas V, J, and C segments are found in each gene, D segments are only present in the IGH, TCR β, and δ genes. The V, D, and J genes are involved in forming the variable region of the Ig and TCR proteins. This region includes the antigen-recognition site. The C region is responsible for other ...

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