Self polysaccharides, lipids, and nucleic acids are T- independent antigens that are not recognized by T cells. These antigens must induce tolerance in B lymphocytes to prevent autoantibody production. Self proteins may not elicit autoantibody responses because of tolerance in helper T cells and in B cells. It is suspected that diseases associated with autoantibody production, such as systemic lupus erythematosus (SLE), are caused by defective tolerance in both B lymphocytes and helper T cells.

Central B Cell Tolerance

When immature B lymphocytes interact strongly with self antigens in the bone marrow, the B cells either change their receptor specificity (receptor editing) or are killed (deletion) (Fig.1).

Fig1. Central tolerance in immature B lymphocytes. An immature B cell that recognizes self antigen in the bone marrow changes its antigen receptor (receptor editing), dies by apoptosis (negative selection, or deletion), or reduces antigen receptor expression and becomes functionally unresponsive. Ig, Immunoglobulin.

• Receptor editing. Immature B cells are at a stage of maturation in the bone marrow when they have rear ranged their immunoglobulin (Ig) genes, express IgM with a heavy chain and light chain, and have shut off the RAG genes that encode the recombinase. If these B cells recognize self antigens in the bone marrow, they may reexpress RAG genes, resume light-chain gene recombination, and express a new Ig light chain (see Chapter 4). The heavy chain gene cannot recombine because some segments are lost during the initial recombination. The new light chain associates with the previously expressed Ig heavy chain to produce a new antigen receptor that may no longer recognize the self antigen. This process of changing receptor specificity, called receptor editing, reduces the chance that potentially harmful self-reactive B cells will leave the marrow. It is estimated that 25% to 50% of mature B cells in a normal individual may have undergone receptor editing during their maturation. (There is no evidence that developing T cells can undergo receptor editing.)

• Deletion. If editing fails, immature B cells that strongly recognize self antigens receive death signals and die by apoptosis. This process of deletion is simi lar to negative selection of immature T lymphocytes. As in the T cell compartment, negative selection of B cells eliminates lymphocytes with high-affinity receptors for abundant, and usually widely expressed, cell membrane or soluble self antigens.

• Anergy. Some self antigens, such as soluble proteins, may be recognized in the bone marrow with low avidity. B cells specific for these antigens survive, but antigen receptor expression is reduced, and the cells become functionally unresponsive (anergic). 

Peripheral B Cell Tolerance

 Mature B lymphocytes that encounter self antigens in peripheral lymphoid tissues become incapable of responding to that antigen (Fig. 2). According to one hypothesis, if B cells recognize a protein anti gen but do not receive T cell help (because helper T cells have been eliminated or are tolerant), the B cells become anergic because of a block in signaling from the antigen receptor. Anergic B cells may leave lymphoid follicles and are subsequently excluded from the follicles. These excluded B cells may die because they do not receive necessary survival stimuli. B cells that recognize self antigens in the periphery may also undergo apoptosis, or inhibitory receptors on the B cells may be engaged, thus preventing activation. As mentioned earlier, regulatory T cells may also contribute to B cell tolerance. 

Fig2. Peripheral tolerance in B lymphocytes. A mature B cell that recognizes a self-antigen without T cell help is functionally inactivated and becomes incapable of responding to that antigen (anergy), or it dies by apoptosis (deletion), or its activation is suppressed by engagement of inhibitory receptors

مواضيع ذات صلة

الحساسية الدوائية نحو العوامل المخصرة للوصل العَصَبِي العَضَلِي

آليات حساسية السلفوناميدات ومظاهرها

Antigen - Antibody Interaction: Specificity and Cross - Reactivity

ANTIBODY SYNTHESIS

Tolerance to Commensal Microbes and Fetal Antigens

Peripheral T Lymphocyte Tolerance

Immune Memory

B Cells

T Cells

إزالَةُ التَحسس نحو البنسلين Penicillin Desensitization

الحساسية نحو البنسلين

الفرق بين فَرْطُ التحسس والحساسية الدوائية