Low-Level Expression of CD138 Marks Naturally Arising Anergic B Cells

Area of Science:

• Immunology
• Cell Biology
• Autoimmunity

Background:

• Autoreactive B cells persist as either immunocompetent or anergic cells, rather than being completely deleted.
• While anergic B cells have been studied in engineered models, characterizing naturally occurring anergic B cells is vital for understanding their role in immune regulation and autoimmune diseases.

Purpose of the Study:

• To identify and characterize naturally occurring anergic B cells in normal mice.
• To investigate the role of CD138 expression as a marker for these anergic B cells.
• To understand the functional and molecular properties of these naturally arising anergic B cells.

Main Methods:

• Flow cytometry was used to identify splenic B cells expressing low levels of CD138 (CD138int).
• Gene expression profiling was performed on CD138int B cells and compared to other B cell subsets (plasma cells, age-associated B cells, germinal center B cells).
• Functional assays measured calcium (Ca2+) response and CD69 upregulation upon B cell receptor (BCR) engagement.
• B cell receptor repertoire analysis was conducted on CD138int and CD138- FO B cells.

Main Results:

• Low-level CD138 expression marks naturally occurring anergic B cells, distinct from plasma cells.
• CD138int B cells include IgMlowIgDhigh follicular (FO) B cells and transitional 3 B cells.
• These cells display an anergic gene expression profile, attenuated Ca2+ and CD69 responses upon BCR stimulation, and a distinct BCR repertoire compared to CD138- FO B cells.

Conclusions:

• Polyclonal anergic B cells, characterized by CD138int expression, exist in normal mice.
• These cells exhibit reduced signaling upon BCR engagement and possess a unique BCR repertoire.
• Understanding these naturally anergic B cells is key to unraveling their contribution to immune homeostasis and autoimmune pathology.