B Lymphocytes: Development and Functions

B Lymphocytes: Development and Functions

  • B lymphocytes secreting plasma cells and thus antibodies are the basic cells of humoral immunity.
  • The normal quantity of B cells in peripheral blood is about 25% (in the range of 18-30%) from total blood lymphocyte population.
  • B lymphocytes are the progenies of hematopoietic stem cells. Their early differentiation occurs in the fetal liver and later in bone marrow, in adults – in bone marrow only.
  • B cells were designated according to the name of the central lymphoid organ of humoral immunity in birds (Fabricius’ pouch or in Latin “bursa Fabricii”). Central lymphoid organ in mammals for B lymphocytes production is bone marrow. It is generally ascertained that the nearest analogue of Fabricius’ pouch in mammals is Peyer’s patches in the intestine.
  • B lymphocytes begin to differentiate from hematopoietic stem cell through the stage of common lymphoid progenitor cell.
  • B cell precursors arise under the influence of growth cytokines (IL-3, IL-7, IL-4, IL-6 and some others).
  • As the final result of development, at least two distinct lineages of mature B cells are generated – minor B-1 subset and the majority of other B lymphocytes sometimes termed as B-2 subset.
  • Most of the B cells (e.g., B-2 subset) undergo antigen-independent differentiation in the bone marrow. It is next followed by their antigen-dependent differentiation after the migration of B cells into B-related zones of peripheral lymphoid tissues.
  • During pregnancy, B cells of the fetus are generated primarily in fetal liver, after birth – in the bone marrow.
  • Early-stage of B cell development or pro-B cell is characterized by activation of recombinase Rag proteins that stimulate rearrangement of immunoglobulin-encoding genes.
  • Subsequent transformation into the pre-B cell is followed by membrane expression of IgM heavy chain (μ-chain) and membrane CD10 and CD19 molecules.
  • The next stage of development creates the immature B cells that carry complete IgM molecule on their surface (antibody B cell receptor or BCR).
  • Immature B cells with BCR demonstrating the high binding capacity to the self-antigens undergo the process of receptor editing. This is followed by reactivation of Rag recombinases of B cells resulting in the additional rearrangement of BCR light chain. This leads to a decrease of BCR binding power against the self-antigens.
  • In case of inefficient receptor editing, the clones of immature B cells retaining BCR with high affinity against the self structures are eliminated by apoptosis (negative selection of autoreactive B cells).
  • The rest of the B cells predominantly migrate to the spleen, where their transformation into follicular mature B cells occurs.
  • Mature B cells simultaneously express two types of membrane BCR of the same specificity – IgM and IgD receptor molecules. They extend their migration to other peripheral B-dependent zones of the lymphoid system (within the spleen, lymph nodes, mucosa-associated lymphoid tissue of gastrointestinal and respiratory tracts, etc.).
  • In peripheral B-dependent zones, mature B lymphocytes commence their antigen-dependent differentiation. They lose surface IgD. After antigen binding to the Ig receptor, B cells undergo blast transformation resulting in clonal expansion of antigen-specific B cell clones.
  • At the end of blast transformation, B lymphocytes change into plasma cells. The latter are secretory cells capable of producing antibodies of the same specificity but only 1 from 5 available Ig classes (IgM, IgD, IgG, IgA, or IgE).
  • B cells require T cell help (Th2) for their appropriate differentiation. Th2 produce IL-4, IL-6 and other cytokines stimulating B cell development. Follicular helper cells drive the transformation of follicular B lymphocytes into long-living antibody-secreting plasma cells and memory B cells.
  • B cells express the number of differentiation markers like CD19, CD20, CD21, CD22, CD40, CD72, receptors to C3b-component of complement, etc.
  • Nevertheless, some antigens with high molecular weight and strong molecular charge (T-independent antigens) can directly stimulate B cells without T cell help. Among these antigens are bacterial polysaccharides and lipids, flagellin proteins, and other similar structures.
  • Most of the B cells responding against T-independent antigens pertain to minor B-1 cell subpopulation, highly present in mucous tissues and body compartments.
  • B-1 cell subset arises earlier in ontogeny than conventional B lymphocytes. They originate from fetal liver-derived hematopoietic stem cells. In mucosal tissues, they demonstrate self-renewal without support from the host bone marrow.
  • After transformation into plasma cells, they produce polyspecific natural antibodies capable of binding to many microbial structures. Natural antibodies pertain mainly to IgM class and to less extent to certain IgG subclasses, e.g., IgG3.
  • They create the first line of body defence against microbial pathogens. However, in some cases, natural antibodies become responsible for autoimmune reactions as a result of their polyspecificity.
  • In addition, at least one-half of IgA-secreting cells of gut mucosa is regarded as derived from the B-1 cell subset.
  • Thus, the B-1 subset is found to be the special B cell population supporting innate humoral immunity.
  • The behaviour, similar to B-1 cell subset, is characteristic also for so-called marginal zone B cells.

B Lymphocytes: Development and Functions