Circulating clonotypic B cells in classic Hodgkin lymphoma

Area of Science:

• Hematology
• Oncology
• Cell Biology

Background:

• Hodgkin and Reed-Sternberg (HRS) cells in Hodgkin lymphoma (HL) are atypical B lymphoid cells.
• The origin and maintenance of HRS cells remain incompletely understood.
• Previous reports suggested a B-cell population generating HRS cells, but this was uncorroborated.

Purpose of the Study:

• To investigate the presence and characteristics of potential HRS cell-generating B-cell subpopulations in HL.
• To determine if such B cells exist in HL patients and share clonality with HRS cells.

Main Methods:

• Analysis of L428 and KM-H2 HL cell lines for distinct B-cell subpopulations.
• Phenotypic characterization of identified B cells using markers like CD27 and aldehyde dehydrogenase (ALDH).
• Assessment of immunoglobulin gene rearrangements in B cells and HRS cells from cell lines and patient blood.

Main Results:

• Rare B-cell subpopulations were identified in both L428 and KM-H2 HL cell lines.
• These B cells expressed immunoglobulin light chain, CD27, and ALDH.
• Clonally related CD27(+)ALDH(high) B cells, sharing immunoglobulin gene rearrangements with HRS cells, were found in the blood of most newly diagnosed HL patients.

Conclusions:

• HL cell lines harbor rare B-cell subpopulations responsible for HRS cell generation.
• Circulating clonotypic B cells expressing CD27 and high ALDH are present in HL patients.
• These findings suggest that circulating clonotypic B cells may be the initiating cells for Hodgkin lymphoma.