Maturation of B cells

• The differentiation of B cells into antibody producing cells is called B cell Maturation.
• During maturation process, the immature B cells develop into mature B Cells.
• By maturation, the B cells gain the ability to produce antibodies. B cell maturation is an antigen dependent process.
• B cell maturation occurs in the secondary lymphoid organs such as spleen, lymph nodes and Peyer’s patches.
• For maturation, the immature B cells of bone marrow leave the bone marrow, migrate through the blood and lymph and reach the secondary lymphoid organs like spleen, lymph nodes and Peyer’s patches. These migrating B cells are called transitional B cells.
• In the lymphoid organs, virgin B cells are exposed to antigens for the first time.
• B cells that encounter antigen for the first time are called naive B cells.
• The B cells recognize the antigens.
• Through antigen recognition, B cells are activated.
• B cells exist as clones. There are about 10⁹ clones of B cells in a body system.
• Each clone is specified for a particular antigen.
• A single B cell clone recognizes a particular antigen. Most of the B cells of that clone differentiate into plasma cells. The plasma cells secrete antibodies
• A few activated B cells of that clone become memory B cells.
• They recognize the same antigen which encounters in future.
• The activated B cells go through affinity maturation and class switching.
• With each encounter, the number of memory cells increases. It is accompanied by affinity maturation which induces the survival of B cells with great affinity for that antigen.
• Naive B cells have IgM and IgD on their surface.
• They have same binding VDJ regions but different constant regions.
• They leave bone marrow with single specificity.
• The naive B cells have very short life. They live only for 3 days to 8 weeks.
• The activated B cells express receptors for IL-2, IL-4, IL-5 and others. These bind to cytokines released by TH cells.
• The pro-B cells develop a B cell marker called B 220 on their surface.
• The pre-B cells develop a surrogate light chain on their surface.
• The immature B cells express on their surface IgM.
• The mature B cells express on their surface both IgM and IgD.
• The early stage mature cells, express low levels of IgD. When these cells reach lymph nodes, the level of IgD increases.
• The activated B cells have IgM, IgD and IgA or IgE.
• The plasma cells have on their surface IgG, IgA, IgE or IgM.

Mechanism of B Cell Maturation

• During maturation the immature B cells are subjected to three important Processes. They are:
• Clonal selection
• Affinity maturation
• Class switching,

Clonal Selection

• The selection of a single lymphocyte (B or T) out of the thousands of lymphocytes by an antigen and its proliferation into a population of similar cells to fight against that antigen is called clonal selection.
• The clonal selection hypothesis was proposed by FM. Burnet, the Nobel Prize winner for his theory.

Mechanism of Clonal Selection

• Thousands of lymphocytes circulate in the blood and lymph.
• Each lymphocyte has a single type of receptor with a unique specificity.
• When an antigen binds to the receptor, the lymphocyte is activated.
• The activated cell undergoes proliferation, producing a population of similar cells, a clone.

• This clone of cells bears identical receptors similar to the parental cell.
• The clone of cells join together and launch a war on the antigen (infection).
• When a B cell is selected, it proliferates into many plasma cells and a few memory B cells.
• The plasma cells and memory B cells have the same type of receptors as their parental cells.
• The plasma cells produce enormous amount of antibodies.
• The memory cells respond in future when there is similar type of infection.

Affinity Maturation

• Affinity maturation is the process of producing antibodies by B cells with increased affinity for antigen.
• With repeated exposures to the same antigen, the host will produce antibodies of greater affinities.

Class Switching

• Class switching is an immunological process by which the antibody produc tion of B cells changes from one class to another class. For example, the change from the production of IgM to IgG.
• It is also called
• Immunoglobulin class switching
• Isotype switching
• Isotypic commutation
• Class switch recombination.

Mechanism of Class Switching

• Class switching starts when the B cell is activated by an antigen.
• This mechanism allows the B cell to produce the required classes of antibodies such as IgA, IgE or IgG.
• Each type of antigen is adapted for a distinct function.
• The function of the antibody is determined by the constant (c) regions of the immunoglobulin.
• Class switching allows different daughter cells from the same activated B cell to produce antibodies of different types.
• The constant region (c) of the antibody heavy chain alone changes during class switching.
• The variable regions remain unchanged during class switching.
• Therefore the antigen specificity also remains unchanged during class switching.
• Thus the progeny of a single B cell can produce antibodies all specific for the same antigen but with ability to fight each antigenic challenge.
• Class switching is triggered by cytokines. Hence the type of antibody generated depends on the cytokines present in the B cell environment.
• Class switching occurs in the heavy chain gene locus by a mechanism called class switch recombination (CSR).
• The CSR mechanism relies on the conserved nucleotide motifs called switch (S) regions found in the DNA upstream of each constant region gene.
• The DNA strand is broken by the activity of a series of enzymes at two selected S regions.
• The variable domain exon is rejoined through a process called non homologous end joining (NHEJ) to the desired constant region.
• This process results in an immunoglobulin gene that encodes antibody of a different type.