B- Cell lymphomagenesis in Non-Hodgkinlymphomas (Part 1)

Abstract

B lymphocytes are essential components of the adaptive immune system, primarily responsible for antibody production. Their development begins in the bone marrow from hematopoietic progenitor cells and proceeds through a series of tightly regulated stages that culminate in their maturation within secondary lymphoid organs, particularly germinal centers. During this process, B cells undergo controlled genetic rearrangements of immunoglobulin genes, somatic hypermutation, and clonal selection (mechanisms critical for generating antigenic diversity and specificity). However, these same processes represent vulnerable checkpoints that can give rise to oncogenic events. B cell lymphomagenesis involves a range of cellular and molecular alterations leading to malignant transformation, with germinal center-derived lymphomas being among the most prevalent forms. Genetic factors such as chromosomal translocations [e.g., t(14;18) leading to BCL2 activation], mutations in cell cycle regulatory genes (including MYC, TP53, and CDKN2A), and aberrant activation of signaling pathways (such as NF-κB and PI3K/AKT) play fundamental roles in this transformation. In addition, epigenetic mechanisms—including aberrant DNA methylation and histone modifications—alter gene expression without changing the DNA sequence, contributing to the loss of cellular control. A comprehensive understanding of these processes is critical for the development of targeted therapies and diagnostic strategies in B cell lymphomas. This publication aims to review the origin, development, and basic functions of B lymphocytes and to analyze the cellular and molecular mechanisms involved in their lymphomagenesis, including the most important genetic and epigenetic factors associated with their malignant transformation.