The B cell receptor (BCR) initiates immune responses through antigen recognition. We report a 3.3-angstrom cryo–electron microscopy structure of human immunoglobulin M (IgM)–BCR in the resting state. IgM-BCR comprises two heavy chains, two light chains, and the Igα/Igβ heterodimer. The ectodomains of the heavy chains closely stack against those of Igα/Igβ, with one heavy chain locked between Igα and Igβ in the juxtamembrane region. Extracellular interactions may determine isotype specificity of the BCR. The transmembrane helices of IgM-BCR form a four-helix bundle that appears to be conserved among all BCR isotypes. This structure contains 14 glycosylation sites on the IgM-BCR ectodomains and reveals three potential surface binding sites. Our work reveals the organizational principles of the BCR and may facilitate the design of antibody-based therapeutics.

中文翻译：

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人 IgM B 细胞受体的冷冻电镜结构

B 细胞受体 (BCR) 通过抗原识别启动免疫反应。我们报告了静息状态下人免疫球蛋白 M (IgM)-BCR 的 3.3 埃低温电子显微镜结构。IgM-BCR 包含两条重链、两条轻链和 Igα/Igβ 异二聚体。重链的胞外域与 Igα/Igβ 的胞外域紧密堆叠，其中一条重链锁定在近膜区域的 Igα 和 Igβ 之间。细胞外相互作用可能决定 BCR 的同种型特异性。IgM-BCR 的跨膜螺旋形成一个四螺旋束，在所有 BCR 同种型中似乎是保守的。该结构在 IgM-BCR 胞外域上包含 14 个糖基化位点，并揭示了三个潜在的表面结合位点。