Immunology: Ontogeny of B and T Lymphocytes

Here is the summary:

• The speaker, Romina, introduces herself as a doctor and researcher at CONICET and the National Academy of Medicine, specializing in immunology and oncology.

• The topic of the lecture is the ontogeny of B and T lymphocytes, specifically how they generate diverse antigen receptors.

• The speaker explains that all blood cells originate from a common precursor cell in the bone marrow, called a stem cell or hematopoietic stem cell.

• From this stem cell, two types of progenitor cells emerge: the lymphoid progenitor cell, which gives rise to B and T lymphocytes, and the myeloid progenitor cell, which gives rise to other blood cells such as granulocytes, macrophages, and dendritic cells.

• The speaker contrasts the strategy of B and T lymphocytes, which recognize antigens through specific receptors, with that of phagocytic cells, which recognize pathogens through pattern recognition receptors.

• Antigens are defined as molecules that can be recognized by B and T lymphocyte receptors, and the portion of the receptor that recognizes the antigen is called the epitope.

• The speaker explains the structure of the B cell receptor, which consists of an immunoglobulin (antibody) attached to the membrane, accompanied by two chains (α and β) that transmit signals and allow the export of the immunoglobulin to the membrane.

• The immunoglobulin is composed of two heavy chains (H) and two light chains (L), with variable regions that recognize antigens and constant regions that determine the class of antibody.

• The variable regions of the heavy and light chains are responsible for antigen recognition, and the specific combination of these regions determines the specificity of the antibody.

• The speaker explains that the generation of diverse antigen receptors is achieved through a process called somatic recombination, where gene fragments are rearranged to create a unique receptor.

• In B cells, this process involves the rearrangement of three gene fragments (V, D, and J) to form the heavy chain variable region, and two gene fragments (V and J) to form the light chain variable region.

• The speaker describes the enzymes involved in somatic recombination, including RAG1 and RAG2, which recognize specific sequences (recombination signal sequences) and cut and rejoin the gene fragments.

• The imprecision of this process generates diversity in the receptor sequence, even when the same gene fragments are used.

• The speaker explains that the process of somatic recombination is guided by recombination signal sequences and that the enzymes involved are not very precise, leading to additional nucleotides being added or removed.

• This generates more diversity in the receptor sequence, even when the same gene fragments are used.

• The speaker also explains the phenomenon of allelic exclusion, where the recombination process works on one chromosome at a time, and if it fails, it tries the other chromosome.

Here is the summary:

• The process of generating diversity in immunoglobulins involves several mechanisms, including the existence of multiple VH segments for heavy chains and Vk and Jk segments for light chains, which can associate with different partners to form different immunoglobulins.

• The process of V(D)J recombination, which generates diversity in immunoglobulins, is a highly stochastic process, meaning it has a high degree of randomness.

• The RAG1 and RAG2 recombinases recognize specific sequences in the DNA and cut them, allowing for the recombination of different segments to form a functional immunoglobulin.

• The process of V(D)J recombination occurs in two stages: first, the heavy chain is formed, and then the light chain is formed.

• If the recombination of the heavy chain is successful, the cell will proliferate, and then the light chain will be recombined independently in each daughter cell.

• The successful recombination of the light chain will lead to the expression of a functional immunoglobulin on the surface of the cell.

• The first immunoglobulin expressed on the surface of the cell is of the IgM class, and it is specific for a particular antigen.

• The process of generating diversity in immunoglobulins occurs before the encounter with the antigen, and it is a mechanism to ensure that the immune system can recognize a wide range of pathogens.

• The ratio of kappa to lambda light chains in a normal individual is 65:35, and this ratio can be used to diagnose certain diseases, such as chronic lymphocytic leukemia.

• The process of generating diversity in immunoglobulins is controlled by mechanisms that ensure that autoreactive cells, which can recognize the body's own antigens, are eliminated or inactivated.

• One of these mechanisms is called central tolerance, which occurs in the bone marrow and ensures that autoreactive cells do not mature and enter the circulation.

• Central tolerance involves the editing of the receptor, which changes the specificity of the immunoglobulin, and the replacement of genes, which also changes the specificity of the immunoglobulin.

• These mechanisms are important to prevent autoimmune diseases, where the immune system attacks the body's own tissues.