Activated B Cells and Plasma Cells Are Resistant to Radiation Therapy

Area of Science:

• Immunology
• Radiation Oncology
• Cancer Biology

Background:

• B cells are crucial for cancer patient outcomes and immunotherapy responses.
• The impact of radiation therapy on B cell populations remains largely uncharacterized.
• Understanding radiation's effects on B cells is vital for optimizing cancer treatment.

Purpose of the Study:

• To characterize the effects of radiation therapy on the development, survival, and phenotype of physiological B-cell subsets.
• To compare the efficacy of focal stereotactic radiation versus large-field radiation in modulating B cell populations.
• To elucidate the mechanisms underlying radiation-induced changes in B cells within the tumor microenvironment.

Main Methods:

• Analysis of B cell subsets in tumor-bearing and non-tumor-bearing mice treated with focal stereotactic or large-field radiation.
• Flow cytometry and real-time reverse transcription polymerase chain reaction (RT-PCR) were employed for detailed B cell subset analysis.
• Immunization strategies were used to assess radiation's impact on B cell activation and class switching.

Main Results:

• Focal stereotactic radiation significantly enhanced the infiltration of B cells, CD8+ T cells, and macrophages into tumors compared to large-field radiation.
• Radiation altered B cell development in bone marrow, increasing early and late pro-B cells and upregulating programmed cell death protein 1 (PD-1).
• Class-switched B cells and plasma cells exhibited high resistance to radiation, upregulating PD-1 ligand 2 (PD-L2) and MHC class II, with Xbp1 and Bcl6 conferring radioresistance in plasma cells.
• Radiation enhanced activation-induced cytidine deaminase (AID)-mediated class switching and somatic hypermutation in primed B cells.

Conclusions:

• Stereotactic radiation therapy is superior to large-field radiation in promoting immune cell infiltration into tumors.
• Plasma cells and class-switched B cells demonstrate significant radioresistance.
• This study provides a comprehensive analysis of radiation's effects on B cells, revealing novel mechanisms of immune modulation within the tumor microenvironment.