Positive and negative selection shape the human naive B cell repertoire.

Area of Science:

• Immunology
• Cell Biology

Background:

• Negative selection of developing B cells is understood, but evidence for naive B cell positive selection is limited.
• The mechanisms governing the naive B cell repertoire remain incompletely elucidated.

Purpose of the Study:

• To investigate the existence and mechanisms of naive B cell positive selection.
• To elucidate the interplay between positive and negative selection in shaping the human B cell repertoire.

Main Methods:

• Utilized two humanized mouse models to study B cell selection.
• Investigated the role of thymus-derived regulatory T cells (Tregs) and MHC class II presentation in negative selection.
• Examined B cells from patients with bare lymphocyte syndrome and utilized HLA-DM inhibition.

Main Results:

• Demonstrated strong skewing of the immunoglobulin repertoire in the peripheral naive B cell pool, indicating positive selection.
• Observed that positive selection in mice mirrored that in human donors and was thymus-independent.
• Confirmed that negative selection of autoreactive B cells requires Tregs and B cell-mediated MHC class II antigen presentation.

Conclusions:

• Both positive and negative selection processes shape the human naive B cell repertoire.
• Positive and negative selection are mediated by distinct molecular and cellular mechanisms.
• Tregs play a crucial role in repressing autoreactive naive B cells.