BCL2 protein expression parallels its mRNA level in normal and malignant B cells

Area of Science:

• Immunology
• Molecular Biology
• Oncology

Background:

• The regulation of B-cell lymphoma 2 (BCL2) protein in germinal center (GC) B cells is debated, with prior studies suggesting posttranscriptional control.
• Recent research has challenged these findings, necessitating further investigation into BCL2 expression regulation.

Purpose of the Study:

• To investigate the regulatory mechanisms of BCL2 protein expression in normal B cells and B-cell lymphoproliferative disorders.
• To clarify whether BCL2 regulation occurs at the transcriptional or posttranscriptional level.

Main Methods:

• Quantitative real-time polymerase chain reaction (PCR) and Standardized Reverse Transcriptase-PCR (StaRT-PCR) were used to measure BCL2 mRNA levels.
• Laser capture microdissection was employed to isolate GC, mantle zone (MNZ), and marginal zone (MGZ) B cells from tonsil samples.
• BCL2 mRNA and protein expression were analyzed in 30 cases of diffuse large B-cell lymphoma (DLBCL).

Main Results:

• GC B cells exhibited low BCL2 transcript levels, correlating with low protein expression, as measured by quantitative RT-PCR on microdissected cells.
• These findings align with results from microarray analyses on fluorescence-activated cell sorter (FACS)-sorted cells and microdissected GC cells.
• A strong correlation between BCL2 mRNA and protein levels was observed in most DLBCL cases.

Conclusions:

• BCL2 protein expression in normal B cells is primarily regulated at the transcriptional level.
• Transcriptional regulation of BCL2 is also the predominant mechanism in the neoplastic cells of most B-cell lymphoproliferative disorders.
• This study resolves controversy regarding BCL2 regulation, supporting transcriptional control in both normal and malignant B cells.