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Opinion Article Open Access

The CD19-Coupled CD21 is an Essential Receptor for B cell Activation

  • 1Department of Immunology and Genomic Medicine, National Jewish Health, Denver, CO 80206, USA
  • 2Department of Immunology and Microbiology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80216, USA
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Corresponding Author

Gongyi Zhang, zhangg@njhealth.org; Gongyi.Zhang@cuanschutz.edu

Received Date: July 24, 2026

Accepted Date: October 15, 2026

Abstract

It has been almost six decades since T cells and B cells were found to be the major players of adaptive immunity. The signal transduction cascades of T cell activation are well studied. However, it is not well appreciated or investigated how the binding of antigens to B cell receptors triggers the downstream signal transduction pathways. It is clear that MHCs with linear antigens presented by antigen-presenting cells (APCs), binding to TCR coupled with CD4/8, is enough to trigger the activation of T cells. For B cells, there are structures of BCRs similar to those of TCRs; however, there are no definitive structures similar to CD4/8 in B cells to help B cell activation. It remains a mystery how B cells are activated by native forms of antigens. Encouraged by our new illustration of the underlying mechanism of T cell activation, a simple model of B cell activation is derived: the CD19-coupled CD21 is an essential receptor for B cell activation.

Keywords

B cell antigen, CD19, CD21, CD22, C3d, CD45, BCR, CD79A, CD79B, Lyn, Syk, PI3K, LAT2

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