Shard background.

Dinis Calado : Areas of interest

Standard content

Our immune system is remarkable. It is composed by a network of cells, including T and B cells that work together to protect our body from infection by pathogens such as bacteria, viruses and parasites.

B cell development and cancer

Figure 1: B cell development and cancer. DNA recombination and mutational processes: VDJ rearrangements (VDJ); somatic hypermutation (SHM); class-switch recombination (CSR).

During an immune response to infection, B cells undergo a T cell dependent stage of development, called germinal centre (GC), essential to produce high affinity antibodies against the pathogen. However, to produce such antibodies, B cells in the GC microenvironment undergo processes of DNA mutation and recombination while rapidly dividing, and infidelity in these processes may lead to oncogenic DNA lesions.

Indeed the most common types of haematological malignancies in adults, such as Hodgkin and non-Hodgkin lymphomas and multiple myeloma, originate from B cells at the GC stage or from B cells that have passed through the GC. This emphasises the importance of the maturation events within the GC microenvironment for B cell cancer development.

Using an integrative approach to immunology and cancer biology, our Laboratory aims to understand the mechanisms by which healthy GC B cells become cancerous.

We use cutting-edge genetic techniques in vivo in the mouse, including conditional gain-of-function and/or loss-of-function specifically in GC B cells using primarily the Cre-LoxP system. The confirmation and/or validation of the findings in these systems are obtained through the study of human samples of GC B cell derived cancers.