Introduction to B Cells also called B-Lymphocytes

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B cells are a type of white blood cell that produce antibodies and play a key role in the humoral immunity component of the adaptive immune system. The name B cell stands for bursa-derived cell, as they were first discovered in the bursa of Fabricius, a lymphoid organ in birds. However, in mammals, B cells originate from the bone marrow, which is the primary site of hematopoiesis and lymphopoiesis.

B cells develop from hematopoietic stem cells (HSCs) that reside in the bone marrow. HSCs are multipotent progenitor cells that can give rise to all types of blood cells, including red blood cells, platelets, granulocytes, monocytes, and lymphocytes. HSCs first differentiate into multipotent progenitor (MPP) cells, which retain the ability to generate both myeloid and lymphoid lineages. MPP cells then further differentiate into common lymphoid progenitor (CLP) cells, which are committed to the lymphoid lineage and can produce either B cells or T cells.

CLP cells that remain in the bone marrow undergo a series of developmental stages to become mature B cells. These stages are marked by various gene expression patterns and immunoglobulin gene rearrangements that result in the generation of a diverse repertoire of B cell receptors (BCRs). BCRs are membrane-bound antibodies that recognize specific antigens and initiate B cell activation and differentiation. Each B cell expresses a unique BCR with a distinct antigen specificity, which is determined by the combination of heavy chain and light chain variable regions.

The main stages of B cell development in the bone marrow are:

  • Pro-B cell: This is the earliest stage of B cell development, characterized by the expression of CD19 and CD45R on the cell surface and the rearrangement of the immunoglobulin heavy chain (IgH) gene locus. Pro-B cells undergo V(D)J recombination, a process that randomly joins one variable (V), one diversity (D), and one joining (J) gene segment from a pool of hundreds of gene segments to form a functional IgH gene. This process generates diversity in the IgH variable region and allows pro-B cells to express a pre-BCR composed of an IgH chain paired with a surrogate light chain on the cell surface.
  • Pre-B cell: This stage is characterized by the expression of CD20 and CD25 on the cell surface and the rearrangement of the immunoglobulin light chain (IgL) gene locus. Pre-B cells undergo VJ recombination, a process that randomly joins one V and one J gene segment from a pool of dozens of gene segments to form a functional IgL gene. This process generates diversity in the IgL variable region and allows pre-B cells to express a mature BCR composed of an IgH chain paired with an IgL chain on the cell surface.
  • Immature B cell: This stage is characterized by the expression of CD21 and CD23 on the cell surface and the cessation of immunoglobulin gene rearrangement. Immature B cells express IgM as their primary BCR and undergo negative selection in the bone marrow to eliminate self-reactive clones. Negative selection involves binding of self-antigens to the BCR and inducing apoptosis, receptor editing, anergy, or ignorance depending on the strength and persistence of the signal. This process ensures central tolerance, which prevents autoimmune responses against self-tissues.
  • Mature B cell: This stage is characterized by the expression of CD40 and MHC class II on the cell surface and the migration to peripheral lymphoid organs. Mature B cells express both IgM and IgD as their primary BCRs and undergo positive selection in secondary lymphoid tissues to encounter foreign antigens. Positive selection involves binding of foreign antigens to the BCR and receiving help from T helper cells to proliferate and differentiate into plasma cells or memory cells. Plasma cells secrete large amounts of antibodies specific for the antigen, while memory cells persist for long-term protection against future exposures.