• Description: CD79A, also known as Igα, is a critical component of the B cell receptor (BCR) complex. This protein associates with CD79B (Igβ) to form the signaling component of the BCR. Upon antigen binding, CD79A becomes phosphorylated, leading to the activation of downstream signaling pathways that promote B cell proliferation, differentiation, and antibody production. Dysregulation or mutations in CD79A can lead to various immunological disorders, including B cell malignancies such as diffuse large B cell lymphoma (DLBCL) and other lymphoproliferative disorders. These abnormalities can result in inappropriate B cell activation, contributing to autoimmune diseases or cancer. Understanding CD79A's role can provide insights into disease mechanisms and potential therapeutic targets.
• Validation: Protein expression analysis showed that human CD79A was exclusively detectable in B cells of homozygous B-hCD79A mice but not in wild-type C57BL/6N mice. Leukocytes cell subpopulation analysis showed that humanization of CD79A does not change the overall frequency or distribution of immune cell types in spleen, blood and lymph nodes. 
• Application: Humanized B-hCD79A mice are valuable for studying human B cell biology, immune responses, and therapies, and can also be used in investigating the efficacy and safety of B cell-targeted therapies towards various B cell-associated disorders.

Gene targeting strategy for B-hCD79A mice. 
The exons 1-3 of mouse Cd79a gene that encode signal peptide and extracellular domain were replaced by human counterparts in B-hCD79A mice. The genomic region of mouse Cd79a gene that encodes transmembrane and cytoplasmic portion was retained. The promoter, 5’UTR and 3’UTR region of the mouse gene were also retained. The chimeric CD79A expression was driven by endogenous mouse Cd79a promoter, while mouse Cd79a gene transcription and translation was disrupted.

Strain specific CD79A expression analysis in wild-type C57BL/6N mice and homozygous humanized B-hCD79A mice by flow cytometry. Spleen was collected from wild-type C57BL/6N mice (+/+) (male, 8-week-old) and homozygous B-hCD79A mice (H/H) (male, 8-week-old). Protein expression in B cells was analyzed with anti-mouse CD79A antibody (Biolegend, 133105) and anti-human CD79A antibody (RD, FAB69201G) by flow cytometry. The anti-mouse CD79A antibody recognized both wild-type mice and humanized mice because its recognition sites were the intracellular region, which was not replaced in the humanized mice. Human CD79A was exclusively in homozygous B-hCD79A mice but not in wild-type C57BL/6N mice .

Mouse CD79B expression analysis in wild-type C57BL/6N mice and homozygous humanized B-hCD79A mice by flow cytometry. Spleen was collected from wild-type C57BL/6N mice (+/+) (male, 8-week-old) and homozygous B-hCD79A mice (H/H) (male, 8-week-old). Protein expression was analyzed with anti-mouse CD79B antibody (RD, FAB6814V) by flow cytometry. Mouse CD79B was both detectable in wild-type C57BL/6N mice and homozygous B-hCD79A mice.

Frequency of leukocyte subpopulations in spleen by flow cytometry. Splenocytes were isolated from wild-type C57BL/6N (+/+) and homozygous B-hCD79A (H/H) (female, n=3, 8-week-old). A. Flow cytometry analysis of the splenocytes was performed to assess the frequency of leukocyte subpopulations. B. Frequency of T cell subpopulations. Percentages of T cells, B cells, NK cells, dendritic cells, monocytes, macrophages, neutrophils, CD4+ T cells, CD8+ T cells and Tregs in B-hCD79A were similar to those in C57BL/6N mice, demonstrating that humanization of CD79A does not change the frequency or distribution of these cell types in spleen. The frequency of leukocyte subpopulations in blood and lymph nodes of B-hCD79A mice were also similar to wild-type C57BL/6N mice (Data not shown). Values are expressed as mean ± SEM. Significance was determined by two-way ANOVA test.  *P < 0.05, **P < 0.01, ***P <0.001.

Homozygotes for targeted null mutations exhibit arrested development of B cells at the pro-B cell stage, leading to loss of mature B cells. (MGI; DOI: 10.1016/j.cell.2004.05.014)