High-Efficiency B Cell Research with the Improved Mb1-iCre Mouse Model

Introduction to Mb1-iCre Mice for B Cell Research

In immunology, B cells are a crucial component of the adaptive immune system. To better understand their function, scientists have developed specialized research tools and models. Among these, the Mb1-Cre mouse has gained prominence for its high recombination efficiency in B cell-specific studies. Codon-improved Cre recombinase (iCre) is an improved version of Cre that's designed to be expressed more efficiently and reduce the likelihood of epigenetic silencing in mammals. Additionally, iCre is expressed at higher levels in mice than P1 bacteriophage Cre, which facilitates high rates of Cre-driven recombination.

Today, we introduce the Mb1-iCre Mouse Model (Product No: C001552), an innovative tool tailored for precise & highly-efficient B cell targeting.

Understanding B Cell Receptors (BCRs)

The B cell receptor (BCR) is a hallmark surface complex of B cells, critical for regulating their survival, adaptation, activation, development, and transformation. The BCR consists of:

1. A membrane-bound immunoglobulin (Ig) molecule non-covalently linked to the

2. Igα (CD79a) and Igβ (CD79b) transmembrane signaling subunits

This complex plays a central role in antigen recognition and the adaptive immune response. When an antigen binds to the BCR, it triggers antigen-induced BCR signaling, activating a series of signal cascades and cellular processes.^[1] 

The MB1 gene (also known as the CD79a gene) encodes the Igα protein–an integral component of the BCR complex–which is exclusively expressed in B cells beginning in the very early pro-B cell stage in the bone marrow.^[3] The Igα protein is primarily expressed in lymphoid follicles and subpopulations of peripheral immune cells, with notable cytoplasmic expression characteristics.

Figure 1. Structure of the B cell receptor (BCR) complex.^[3]

Mb1-iCre Mouse Model: Features and Benefits

Cyagen has independently developed the Mb1-iCre Mouse Model (Product No: C001552) using advanced gene editing techniques. This model incorporates a codon-optimized iCre recombinase element with high recombination activity that was knocked into the endogenous Cd79a gene of mice, enabling its specific expression in B cells. This model generation strategy disrupts the expression of the mouse's endogenous Cd79a gene, ensuring highly efficient recombination activity in B cells.

When Mb1-iCre mice are bred with mice carrying loxP-flanked sequences, the offspring may undergo Cre-mediated recombination that occurs predominantly in B cells. Notably, the Cre recombinase activity is higher in the early stages of B cell development.

1. Cre recombinase activity in lymphoid B cells

To assess the efficiency of Cre recombination in B cells, Mb1-iCre mice were crossed with ROSA26-LSL-tdTomato mice, which express tdTomato fluorescent protein conditionally.

Figure 2. Expression of Cre recombinase in lymphoid B cells (mCD45+ mCD19+) in peripheral blood, spleen, and bone marrow.

Mating the Mb1-iCre mice with ROSA26-LSL-tdTomato mice yielded offspring from which peripheral blood, spleen, and bone marrow tissues were collected. TdTomato protein expression was detected by fluorescence-activated cell sorting (FACS). Flow cytometry (FACS) analysis revealed:

• Peripheral Blood B Cells: Strong tdTomato expression in the peripheral blood lymphoid B cells of Cre+ mice (Mb1-iCre[KI/+];ROSA26-LSL-tdTomato[CKI/+]), with a recombination efficiency of over 98%.
• Splenic Lymphoid B Cells: Recombination efficiency in was approximately 80%
• Bone marrow lymphoid B cells: Recombination efficiency ranged from 76.93% to 80.66%.

2. Cre Recombination Activity in Lymphoid T Cells

Figure 3. Expression of Cre recombinase in lymphoid T cells (mCD45+ mCD3+) in peripheral blood, spleen, and bone marrow.

In contrast, minimal Cre activity was observed in T cells. FACS results showed that in Cre+ mice:

• Peripheral Blood T Cells: 1.89%-2.21% tdTomato expression.
• Splenic T Cells: 2.49%-3.72% tdTomato expression.
• Bone Marrow T Cells: No significant tdTomato expression detected in CD3+ T cell populations.

Conclusion

The Mb1-iCre Mouse Model (Product No: C001552) demonstrates exceptional specificity and recombination efficiency in lymphoid B cells. It serves as an invaluable tool for tissue-specific research targeting lymphoid B cells, ensuring precise genetic modifications.

Alongside our Mb1-iCre mice, Cyagen offers a broad range of inducible Cre mouse models designed to target specific cell types and tissues, supporting diverse research needs across immunology, hematopoiesis, and metabolism. Below is a list capturing some of our newly available Cre, iCre & CreERT2 mouse models alongside their specific tissue/cell applications: