*2.2. B Lymphocytes*

B lymphocytes (B cells) are part of the humoral component of the adaptive immune system and specialised in secreting antibodies. B cells can also present antigens and secrete cytokines. In mammals, B cells mature in the bone marrow, and B cell receptors (BCRs) mature on their cell membranes, which allow B cells to bind specific antigens initiating an antibody response. Such antigen recognition can happen through either low- or high-affinity binding modes [23]. After maturation, multiple subsets of B-cells co-expressing IgM and IgD emerge from the bone marrow and colonise compartments of secondary lymphoid organs [24].

B cell subpopulations can be distinguished in peripheral blood based on surface-marker expression, which mainly represents different developmental stages of the cell. Alterations in some of these populations have been associated with clinical phenotypes in immunodeficiency and autoimmune diseases. The second phase of B-cell development occurs after the antigen-dependent phase. Depending on various contacts and cytokine stimuli received by the activated cell, it will become either a memory cell to be activated once again in the future or it will become a plasma cell producing large amounts of antibodies [25].

Didactically, B cells can be subdivided as follows: plasmablasts (the immature precursor of plasmacytes), plasma cells (antibody-secreting cells arising from B cell differentiation), memory B cells (B2 cells and synonymous with classical B cells), marginal zone (MZ) B cells (specialized population of B cells that are located in the marginal zone of the spleen), B1 cells (subtype of B cells that are distinct from classical B cells with respect to their phenotype, distribution in the body, and function). Unlike classical B cells, B-1 cells are considered functionally to be part of the innate immune response [26]. Regulatory B cells (Breg) negatively regulate the immune response by producing regulatory cytokines and directly interacting with pathogenic T cells via cell-to-cell contact [27].

Abnormal B-cell recognition of self-antigens may lead to autoimmunity, which results in autoantibody production. Autoantibodies produced by B-cell-derived plasma cells provide diagnostic markers for autoimmunity, and also contribute significantly to disease pathogenesis [28]. Autoimmune diseases where B-cell functions are closely correlated with disease activity include systemic lupus erythematosus, rheumatoid arthritis, scleroderma, type 1 diabetes, and multiple sclerosis [28].

### *2.3. T and B Lymphocytes in Periodontal Homeostasis*
