Cryo-EM structures of two human B cell receptor isotypes

Area of Science:

• Immunology
• Structural Biology
• Biochemistry

Background:

• The B cell receptor (BCR) complex is crucial for B cell development and immune responses.
• The molecular mechanisms governing BCR complex assembly are not well understood.

Purpose of the Study:

• To determine the cryo-electron microscopy (cryo-EM) structures of human immunoglobulin G (IgG)-BCR and immunoglobulin M (IgM)-BCR complexes.
• To elucidate the structural basis of BCR complex assembly.

Main Methods:

• Cryo-electron microscopy (cryo-EM) was used to determine the structures of human IgG-BCR and IgM-BCR.
• Analysis of the interactions between membrane-bound immunoglobulin (mIg) and Igα/β subunits.

Main Results:

• The structures reveal a 1:1 stoichiometry between mIg and Igα/β subunits in both IgG-BCR and IgM-BCR.
• BCR assembly involves interactions within extracellular, membrane-proximal, and transmembrane domains.
• Conserved hydrophobic and polar interactions stabilize the transmembrane helices of mIgG/mIgM with Igα/β.
• Distinct head-to-tail and side-by-side modes of interaction were observed between IgG-Cγ3/IgM-Cμ4 domains and Igα/β extracellular domains.

Conclusions:

• This study provides the first structural insights into the assembly of human IgG-BCR and IgM-BCR complexes.
• The findings reveal the structural basis for BCR assembly, offering potential insights into BCR triggering mechanisms.