Within the human immune system, B cells serve as core members of adaptive immunity, constructing a long-term defense against pathogens through antibody production and immune memory formation. Their development proceeds in a strictly ordered manner, while the diversity of functional subsets endows immune responses with exceptional flexibility and specificity. This article will delve into the developmental stages of B cells, key regulatory mechanisms, and the classification and characteristics of functional subsets.
I. B Cell Development: A Multi-Stage Journey from Bone Marrow to Periphery
B cell development originates from hematopoietic stem cells (HSCs) in the bone marrow, undergoing a series of gene rearrangements and phenotypic changes to ultimately differentiate into mature B cells. This process can be divided into the following critical stages (Figure 1):
1. Pro-B cells: At this stage, V(D)J recombination of immunoglobulin heavy chain (IgH) genes occurs, forming functional heavy chains. Studies indicate that pro-B cells retain minimal HSC characteristics when participating in mitochondrial autophagy pathways (e.g., the Pink1/Park2 pathway), suggesting they have entered lineage commitment[1].
2. Pre-B cells: Cells that successfully express IgH proliferate and form pre-B cell receptors (pre-BCRs), with light chain genes initiating rearrangement. Single-cell sequencing reveals that pre-B cells specifically express 203 circular RNAs (circRNAs), potentially involved in regulating the cell cycle[2].
3. Immature B cells: After completing light chain rearrangement, cells express intact BCRs (IgM) on their surface but must undergo negative selection to eliminate self-reactive clones. At this stage, 219 circRNAs are significantly enriched in the cell transcriptome[2].
4. Mature B cells: These migrate to the spleen or lymph nodes and further differentiate into follicular B cells (FO B cells) or marginal zone B cells (MZ B cells). Mature B cells specifically express 207 circRNAs, which may participate in maintaining their homeostatic functions[2].
Notably, B cell development is intricately regulated by transcription factor networks. For example, Bcl6 influences the differentiation of memory B cell subsets (e.g., CD62L+ memory B cells) by regulating genes such as Bcl2 and Zeb2; its overexpression impairs the development of CD62L+ memory B cells[3][3].
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