The Role of Pre-B Cell Receptors in the Light Chain Rearrangement in HUG1 Transgenic Mice

Abstract

Antibodies, also known as immunoglobulins (Igs), are a critical component of the body's ability to produce specific immune response. Produced by B lymphocytes (B cells), each Ig consists of two identical heavy chains (H-chains) and two identical light chains (L-chains). Gene rearrangement during the differentiation/maturation of B cells is central to producing incredible diversity among Igs, thus enabling our body to defend itself against the myriad of foreign substances (antigens) that we encounter each day. The normal sequence of H-chain rearrangement followed by L-chain rearrangement suggests that H-chain rearrangement stimulates the subsequent rearrangement of the L-chain. We have inserted a chimeric transgene called Human Immunoglobulin g1 (HUG-1), consisting of a human constant region (C) and a murine variable region (VDJ) into mice. HUG-1 mediates allelic exclusion of the endogenous H-chain, but does not prompt the production of a rearranged L-chain. For this reason, we believe that the mechanism for the production of a rearranged L-chain is distinct from the production of a rearranged H-chain. In order to better understand the regulation of L-chain production, we want to identify and define the roles of the components of a functional pre-B cell receptor (pre-BCR) that induces L-chain rearrangement. Comparing the proteins associated with a functional pre-BCR and the proteins associated with HUG-1 pre-BCR (in which a critical component signaling for L-chain reproduction is absent or additional components impede signaling) allows us to identify the integral elements of a pre-BCR.