B cell r
Abstract
Receptor editing is the process of ongoing antibody gene rearrangement in a lymphocyte that already has a functional antigen receptor. The expression of a functional antigen receptor will normally terminate further rearrangement (allelic exclusion). However, lymphocytes with autoreactive receptors have a chance at escaping negative regulation by “editing” the specificities of their receptors with additional antibody gene rearrangements. Nemazee points out, “receptor editing separates receptor selection from cellular selection.”1 As such, editing complicates the Clonal Selection Hypothesis, because edited cells are not simply endowed for life with a single, invariant antigen receptor.2 For example, an edited B cell changes the specificity of its B cell receptor (BCR), and if the initial immunoglobulin gene is not inactivated during the editing process, allelic exclusion is violated, and the B cell can exhibit two specificities. Here we will describe the discovery of editing, the pathways of receptor editing at the heavy (H) and light (L) chain loci, and current evidence regarding how and where editing happens and what effects it has on the antibody repertoire.
Scope of review and a word about editing nomenclature
This review focuses on receptor editing and receptor revision in normal and autoimmune B cells of mouse and man. Table 1 provides a glossary of terminology. Terminology that is defined in Table 1 is given in italics the first time it is used. Table 2 summarizes different methods that have been used to analyze editing.
Germline antibody genes undergo primary somatic gene rearrangement (also known as V(D)J recombination) in order to generate the antibody repertoire. This first attempt may be productive (resulting in a functional H chain, H+, or functional L chain, L+) or non-productive (H− or L−). Secondary rearrangement refers to one or more rearrangements that occur after primary rearrangement. Included amongst secondary rearrangements are those that rescue B cells with non-productive primary rearrangements and those that alter BCR specificity. Secondary rearrangements can occur on the same or a different chromosome from the primary rearrangement. Rearrangements that alter the specificity of the BCR to avoid autoreactivity are referred to as receptor editing and usually occur early during B cell development, typically in the bone marrow. Secondary rearrangements that occur in mature B cells are referred to as receptor revision and their effects on autoreactivity are controversial.
Continued at Resource.
.