Introduction

Structure

The BCR consists of a membrane-bound immunoglobulin (mIg) and two signal-transducing subunits, Igα and Igβ. The mIg consists of two heavy chains and two light chains. Antigen binding at the binding site triggers signal transduction by Igα and Igβ. Both consist of an extracellular, Ig-like domain, and an intracellular immunoreceptor tyrosine-based activation motif. ^[1].

Antigen Binding Site

Heavy Chain Interactions (Igα and Igβ)

While the antigen binding site structure of the mIgM BCR is identical to other common soluble antibodies, there are several intracellular interactions between the heavy chains and Igα/β subunits that make it unique. In the Fc portion of the structure, the two heavy chains interact via a disulfide bond and form an . Additionally, the Fc portion binds the with 1:1 stoichiometry. ^[2]. Due to the orientation of the heavy chains in the O-shaped ring, only Heavy chain 1 (Hc1) forms direct interactions with the Igα/β heterodimer. Furthermore, through two hydrogen bonds (T75-Q487 and N73-Q493) which are stabilized by sandwiching of aromatic residues (W76 sandwiched between F358 and F485). Similarly, through three hydrogen bonds (Y66-R491, K62-T530, and R55-T533,). The residues involved in the interactions at the heavy chain and Igα/β interface are highly conserved across all species, suggesting a conserved mode of interaction. ^[1]. The Igα/β heterodimer is an obligate component of all BCRs. Igα and Igβ non-covalently associate with mIgM, and are crucial components for initiating biochemical signaling inside the B cell upon antigen binding. ^[2]. by a disulfide bond between cystine residues (C119-C136). The disulfide bond is stabilized by π-π stacking (Y122 and F52) and a hydrogen bond (G120-R51). These residues are highly conserved across species, suggesting conservation of the Igα/β interface.

Transmembrane Interactions

Function

Proposed Conformational Changes

^[1].

Signal Pathway