The B cell antigen receptor (BCR) plays an essential role in all phases of B cell development. Here we show that the extracellular domains of murine and human Igβ form an I-set immunoglobulin-like structure with an interchain disulfide between cysteines on their G strands. Structural and sequence analysis suggests that Igα displays a similar fold as Igβ. An Igαβ heterodimer model was generated based on the unique disulfide-bonded Igβ dimer. Solution binding studies showed that the extracellular domains of Igαβ preferentially recognize the constant region of BCR with μ chain specificity, suggesting a role for Igαβ to enhance BCRμ chain signaling. Cluster mutations on Igα, Igβ, and a membrane-bound form of immunoglobulin (mIgM) based on the structural model identified distinct areas of potential contacts involving charged residues on both subunits of the coreceptor and the Cμ4 domain of mIgM. These studies provide the first structural model for understanding BCR function.
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We would like to thank Marina Zhuravleva and M. Gordon Joyce for their help in data collection. The use of the Advanced Photon Source was supported by the U.S. Department of Energy, Basic Energy Sciences, Office of Science, under contract W-31-109-Eng-38. This work is supported by intramural research funding from the National Institute of Allergy and Infectious Diseases.