hello in this video we're going to look at and the B cell and the T cell story so the story of the B and T cells as well as we will introduce lymphoma particularly the b-cell lymphoma so just introducing the organs here that are associated with the B and T cells we have the bone marrow the thymus and the lymph node now in the bone marrow there are lymphoid progenitor cells which can either become a precursor T cell or a precursor B cell let us follow the precursor T cells the precursor T cells will move into the thigh the thymus where they become family sites double negative they are double negative because they are there negative for both cd4 and cd8 receptors in the thymus however the double negative thymocytes will develop to become either a CD a cd8 naive T cell which will have the cd8 receptor or a cd4 naive T cell with a cd4 receptor the naive cd4 and cd8 T cells will also have a t cell receptor on them and the naive cd4 naive T cells will then move into the lymph node ready to become activated now let us look to the bone marrow and follow the precursor B so with the help of the enzyme rag1 and to the precursor b cell in the bone marrow will undergo vdj recombination of light and heavy chains to form a naive B cell with a membrane bound IgM antibody so the naive B cell actually will have a unique you can say a specific type of antibody on its surface for a specific type of antigen so the night B cell will leave the bone marrow and proceed to the lymph node during circulation or within the lymph node the naive B cell if the naive B cells IgM surface surface bound IgM recognizes an antigen it will phagocytize it and then present the antigen on an MHC class 2 molecule on its cell surface now the expand the experienced naive b-cell now waits for either co-stimulation or stimulation by a activated cd4 t-cell so we're going to look at what happens in co-stimulation so let us just say this naive cd4 T cell can recognize the antigen being presented by the B cell what happens next is called co-stimulation the naive cd4 T cell stimulates the naive B cell and the naive B cell stimulates the cd4 T cell alternatively alternatively what could have happened is that a fully activated cd4 t-cell could have activated the naive B so but anyways what we end up with is an activated cd4 T cell and an activated b-cell when the B cell is activated by the T cell something big happens there are cytokines that the T cell will secrete that trigger the naive B cell to proliferate into central blasts during the proliferation process each individual b-cell undergoes what is known as somatic hypermutation by the AI D enzyme somatic hypermutation introduces point mutation in the variable region of the antibody gene thus what we end up with are we end up with many central blasts each with different surface IgM antibodies because they're variable regions have slightly changed thanks to the mutations so these central blasts can have antibodies with either an increased or decreased affinity to that antigen the central blasts then move through the germinal Center to where there are many follicular dendritic cells presenting many antigens on its surface there are also follicular T helper cells in this area when the central blasts move from one part of the germinal center to the other they become central sites and these central sites need cytokines in order to survive and mature so they sample these antigens presented by the genetic cells using their newly acquired specific surface AGM antibody unfortunately some central sites will have decreased affinity to these antigens after undergoing somatic hypermutation the ones that have decreased affinity will die through apoptosis fortunately however there are central sites that will have an increased affinity following hypermutation and so will easily recognize the antigen presented by the follicular dendritic cell so if these central sites recognize the antigen it will again engulf it and present it to the T helper follicular cell nearby the T helper follicular cell will now help help the B cell help the center side which is the B cell help the central site to proliferate and then to differentiate this Center site can differentiate into memory B cell or into a plasma blast which will then become a plus plasma cell plasma cell are the type of B cells that secrete antibodies when the central site receives signals by the from the T cells to differentiate the central sites actually undergo class switching which is basically where the constant region of the of the other of the antibody can can become a specific class so it can change into an IgE IgA or IgG for example now I hope that made sense um I also we also have to introduce the thymic B cells which are B cells that reside in the thymus but we will not go into the functions and the thymic B cells here okay so what you have watched till now was an overview overall picture sorry of the T cell and particularly the B cell story now we will start looking at lymphoma which as the name suggests is tumor of the lymph lymphoma involves cancer cells coming from mainly T or B cell development so using this diagram we can see in which steps of the T and B cell development these cancers these cancer cells may arise from and what type of lymphoma can result so lymphoma lymphoma is a heterogeneous group of malignancies characterized by proliferation of lymphoid tissue diverse and they are diverse in cellular origin morphology immunophenotype Saito Saito Saito genetic and molecular abnormalities and they're different in response to treatment and prognosis so their big deal lymphoma can be categorized into two broad categories these are Hodgkin's and non-hodgkins lymphoma in this video we will focus on non-hodgkins lymphoma which is the sixth most frequent cancer and it is increased and it is increasing in prevalence risk factors for non-hodgkins lymphoma include in me neurological disturbances viral genetic and environmental so illogical can be HIV or autoimmune diseases which predisposes one to lymphoma viruses such as HIV epsilon bar virus and HCV are risk factors also for lymphoma genetics as in Klinefelter's and skid increases the risk of non-hodgkin lymphoma and environmental risk factors include pesticides herbicides and smoking okay now let us look at the different types of non-hodgkins lymphoma and where they can arise from so non-hodgkins lymphoma can either be can either be b-cell or t cell in origin we will first look at the T cell non-hodgkins lymphoma so T cells in the thymus during its development can give rise to precursor T cell lymphomas which we won't go into similarly T cells that have moved into the lymph node can give rise to what's called the peripheral T cell lymphomas the near plasma now t-cell lymphomas can arise during genetic rearrangement of the t-cell receptor and during positive and negative selection in the thymus which will lead to either precursor or peripheral t-cell lymphomas of course that's like that was just super basic overview now what is important to know is that t-cell lymphomas are less common than b-cell lymphomas so we were just so we just looked at two types two to two classes you can say of t-cell lymphomas now let us focus on b-cell lymphomas and we'll go into more detail we will focus more on the b-cell lymphomas because as I mentioned just then the prevalence of the b-cell lymphoma is much higher than the t salt and this is because B cells undergo so many genetic changes during its development naive b-cells can give rise to mantle cell lymphoma B cells that have experienced an antigen encountered can become a chronic lymphocytic leukemia or small in first lymphocytic lymphoma lymphoma and leukemia can often be confusing they are different yet related the main difference is a leukemia involves the blood anyways we won't really talk about Leukemia and Lymphoma in this video but it's just good to know that this particular part of the B cell development can lead to the chronic lymphocytic leukemia or the small lymphocytic lymphoma the central blasts in the germinal Center can give rise to Burkitt's lymphoma and germinal Center be like diffuse large b-cell lymphoma or DLBCL which has interestingly 60% five-year survival both Burkitt's lymphoma and germ cell be like diffuse large b-cell lymphoma are some of the common types of b-cell lymphomas because possibly because of the genetic mutation that occurs following somatic hypermutation in the germ germinal center so what I mean is that following hyper mutation in the germinal Center which is a normal process it can lead to mutations leading to cancer which is the Burkitt's lymphoma or the large b-cell large diffuse b-cell lymphoma the central sites can give rise to follicular lymphoma memory b-cells following class switching which is another genetic rearrangement can give rise to chronic lymphocytic leukemia or the small lymphocytic lymphoma as we've already introduced earlier plasma blasts can give rise to activated b-cell like diffuse large b-cell lymphoma which has a 35% 5-year survival so now we have actually talked about two types of diffuse large b-cell lymphoma well we actually have three and the third one arises from the thymic b-cells so here the thymic b-cells can give rise to what is called the primary mediastinal be cell-like diffuse large b-cell lymphoma so we have one two three types of diffuse large b-cell lymphoma anyways the reason it is important to know that to know this is because the most common non-hodgkins b-cell lymphoma are the diffuse large b-cell lymphomas as well as the follicular lymphoma x' so that is why it's important to know these so those were the major types of lymphomas I wanted to talk about but using this diagram it is also important to introduce a common type of cancer which arises from one of one one particular cell which are the plasma cells plasma cells can give rise to multiple myeloma in which there are so much there's so much plasma cells being produced and moving into the bone marrow that it causes big problems and I will have a video on that hopefully a link to the video hopefully so so far we've talked about the bead and t-cell story and we've introduced the different types of lymphomas now let us look at the the reason why they arise so I guess the molecular aspect of this of lymphoma which is important so we just looked at the T and the B cell story as well as a different types of non-hodgkins lymphoma that can arise during different periods of the development of the B and T cells now let us look at some now let's look at the pathophysiology basically how do these lymphomas arise and they basically arise mainly through genetics genetic changes such as one translocation and two mutations during development during a like somatic hypermutation for example or class switching so the translocations of chromosomes are seen in many of the lymphomas translocation of for example the BC bcl-2 and bcl6 genes are seen in a lot of lymphomas and also we can see mutations and amplifications of certain genes such as mutations in the p53 gene the bcl-2 the bcl6 and the myc genes so that's so just overall know that lymphomas arise from genetic changes such as translocations and mutations during the during the development of the cells thank you for watching I hope you enjoyed this video