How do B lymphocytes work?
I'm confused. How can a b cell recognize an antigen it's never experienced before? Do the immature cell just make all kind of crazy receptors at random (with the hopes of becoming useful)? Is this for all epitopes or just a few? What am I missing here?
Also, how can the immune system build specific antigens to tentative invaders (or does it)?
My current understanding is:
-Many antibody templates exist.
-Some of these fit certain ag's better than others.
-These ab's are adapted (how?) to fit the ag better and the getting used to is remembered by the B cells.
Is this even close? If so, what am I missing and by what operation are the adaptations developed? thanks.
Answers:
Yep it sure is confusing at first - but outstandingly interesting.
During their development each B cell acquires the fitness to produce one kind of antibody and that becomes its antigen receptor. So there are loads of 'templates' - give or take a few 100 million different B cells. That should be enough to cover pretty much anything we are exposed to during a lifetime.
Once a 'bug' comes along only a few of our B cell will recognise it and when some of those B cells bind to the bacteria they are triggered to activate. They enlarge and divide and produce clones of themselves that can trade name the same antibody they make (clonal selection). *
Some of these cells become 'effector cells' or 'plasma cells' that actively face-off the infection and others become 'memory cells' held in reserve for fast action should that same germs invade again in the future.
When the infection is over the plasma cells die but the memory cell continue to circulate in the body, ready to pounce on a remembered bacterium. There are presently way more B cells that 'know' that infection - put in other jargon the body has adapted.
* When a B cell recognises an antigen, it is stimulated to divide (or proliferate). During proliferation, the B cell receptor locus undergoes an extremely high rate of somatic mutation, that is to say at far far greater than the normal rate of mutation across the genome. The mutations that occur are mainly single floor substitutions, with occasional insertions and deletions and occur at “hotspots” located throughout DNA that encodes the immunoglobulin undependable region. This directed hypermutation allows for the selection of B cells that express immunoglobulin receptors possessing an enhanced ability to recognise and bind a specific foreign antigen. This give even more variability to the system.
Wow great isn't it ! Source(s): Intro to Micro - Ingraham & Ingraham
Wikipedia
Also I have a MMedSc
All of your assumptions are not far from reality but surrounded by different stages and processes. To be able to finally produce and release amounts of soluble antibodies, B cells go through a series of change and mechanisms in different parts.
Naive B cells (not exposed to any foreign antigen) seasoned in the bone marrow. There, B cells develop specific receptors situated in their membranes (which are structurally equal to soluble M and D antibodies). To express these molecular receptors, B cell must experience "genetic recombinations" in the corresponding genes (the genes codifing the receptors). The recombination is a complex process, it's executed by enzymes called recombinases and as you said the process is done randomly and thus generate molecules in the hope of becoming useful (you couldn't have said it better).
The maturation of B cell in the bone marrow makes the B cells tolerant to antigens present within the human cells, this is another complex sequence but basically, B cells are exposed to lots autoantigens present in the bone marrow's stroma, when the B cell recognizes one of this it's eliminated and this instrument preventing autoinmune responses. There are also periphery tolerance mechanisms outside bone marrow but this is another story.
Surviving naive B cells (very few from the untested count) continue their maturation in the spleen and once mature, they express fitfully created B receptors (BCR) and each naive B cell have one different B receptor type, competent to detect different possible antigens but not able to detect human cells antigens.
These mature optimistic B cells then abandon the spleen and bone marrow and migrate to the limph nodes and limph tissues surrounded by the body.
Patogens and their antigens, normally infect periphery tissues and their antigens are transported through the limph vessels to the limph nodes and once there, these antigens are exposed to thousands of optimistic B cells, each cells near one type of BCR. When a BCR recognizes an antigen, the B cell migrate to other part of the lymph node where nearby are T helper cells and start to proliferate. Since all descendants will contain impossible to tell apart gene recombination pattern as the original B cell (the one that recognized the antigen) they will also express alike BCR and are all called clones and this process is called "clonal expansion", to finally know how to differentiate into effector cells and produce soluble antibodies (which are BRC but released outside the cell) they need some interactions with T PA lymphocytes. These are activated by a different mechanism, unlike B cells they don't endorse soluble antigens and are activated only when an antigen presenting cell expose them through the MHC (mayor histocompatibility complex) a processed antigen captured surrounded by the periphery and transported to the limph node, these APC in the periphery are called dendritic cells. It turns out that the B lymphocytes are also antigen presenting cell and once it recognizes the antigen they also process them and expose epitopes of the antigen to a previously activated T cell. For the cooperation between B and T cells to be succesful it's not necesary that both authorize the same epitope (since B's recognize epitopes present in soluble antigens and T cell recognize epitopes from the processed antigens) but they must recognize epitopes of the same antigen. When this occur, the T cell express chemical factors that induce the proliferation of the B cell. Some B cells (all clones producing the same BCR and antibodies) consequently differenciate into plasma cells able to produce large amounts of soluble M antibodies. Some B cell then, experience another complex process called "somatic hypermutation" which allows them to mature even more their affinity by their antigen and next change the type of antibody produced, then they differentiate into plasma cells but producing G isotype antibodies.
Some of these B cell resulting from somatic hypermutation don't differentiate to plasma cells instead they migrate through tissues and the bone marrow waiting for the antigens, these are called B memory cell.
By the way.., you said contained by one of your statements, "many antibody templates exist", this is not part of an adaptative immune response but the statement is true. There are B lymphocytes call B1 cells producing antibodies to antigens never exposed to. These are called natural antibodies specially adjectives for certain capsulated bacterias. Very young childs have this T independent imperviousness (B1 cells don't need antigens or T helper cell colaboration to produce antibodies) not totally developed and this is a reason why childs are more susceptible to infections by these patogens like Haemophilus influenza, Streptococcus pneumoniae etc specially until 2 years of age. Source(s): immunology classes
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Also, how can the immune system build specific antigens to tentative invaders (or does it)?
My current understanding is:
-Many antibody templates exist.
-Some of these fit certain ag's better than others.
-These ab's are adapted (how?) to fit the ag better and the getting used to is remembered by the B cells.
Is this even close? If so, what am I missing and by what operation are the adaptations developed? thanks.
Answers:
Yep it sure is confusing at first - but outstandingly interesting.
During their development each B cell acquires the fitness to produce one kind of antibody and that becomes its antigen receptor. So there are loads of 'templates' - give or take a few 100 million different B cells. That should be enough to cover pretty much anything we are exposed to during a lifetime.
Once a 'bug' comes along only a few of our B cell will recognise it and when some of those B cells bind to the bacteria they are triggered to activate. They enlarge and divide and produce clones of themselves that can trade name the same antibody they make (clonal selection). *
Some of these cells become 'effector cells' or 'plasma cells' that actively face-off the infection and others become 'memory cells' held in reserve for fast action should that same germs invade again in the future.
When the infection is over the plasma cells die but the memory cell continue to circulate in the body, ready to pounce on a remembered bacterium. There are presently way more B cells that 'know' that infection - put in other jargon the body has adapted.
* When a B cell recognises an antigen, it is stimulated to divide (or proliferate). During proliferation, the B cell receptor locus undergoes an extremely high rate of somatic mutation, that is to say at far far greater than the normal rate of mutation across the genome. The mutations that occur are mainly single floor substitutions, with occasional insertions and deletions and occur at “hotspots” located throughout DNA that encodes the immunoglobulin undependable region. This directed hypermutation allows for the selection of B cells that express immunoglobulin receptors possessing an enhanced ability to recognise and bind a specific foreign antigen. This give even more variability to the system.
Wow great isn't it ! Source(s): Intro to Micro - Ingraham & Ingraham
Wikipedia
Also I have a MMedSc
All of your assumptions are not far from reality but surrounded by different stages and processes. To be able to finally produce and release amounts of soluble antibodies, B cells go through a series of change and mechanisms in different parts.
Naive B cells (not exposed to any foreign antigen) seasoned in the bone marrow. There, B cells develop specific receptors situated in their membranes (which are structurally equal to soluble M and D antibodies). To express these molecular receptors, B cell must experience "genetic recombinations" in the corresponding genes (the genes codifing the receptors). The recombination is a complex process, it's executed by enzymes called recombinases and as you said the process is done randomly and thus generate molecules in the hope of becoming useful (you couldn't have said it better).
The maturation of B cell in the bone marrow makes the B cells tolerant to antigens present within the human cells, this is another complex sequence but basically, B cells are exposed to lots autoantigens present in the bone marrow's stroma, when the B cell recognizes one of this it's eliminated and this instrument preventing autoinmune responses. There are also periphery tolerance mechanisms outside bone marrow but this is another story.
Surviving naive B cells (very few from the untested count) continue their maturation in the spleen and once mature, they express fitfully created B receptors (BCR) and each naive B cell have one different B receptor type, competent to detect different possible antigens but not able to detect human cells antigens.
These mature optimistic B cells then abandon the spleen and bone marrow and migrate to the limph nodes and limph tissues surrounded by the body.
Patogens and their antigens, normally infect periphery tissues and their antigens are transported through the limph vessels to the limph nodes and once there, these antigens are exposed to thousands of optimistic B cells, each cells near one type of BCR. When a BCR recognizes an antigen, the B cell migrate to other part of the lymph node where nearby are T helper cells and start to proliferate. Since all descendants will contain impossible to tell apart gene recombination pattern as the original B cell (the one that recognized the antigen) they will also express alike BCR and are all called clones and this process is called "clonal expansion", to finally know how to differentiate into effector cells and produce soluble antibodies (which are BRC but released outside the cell) they need some interactions with T PA lymphocytes. These are activated by a different mechanism, unlike B cells they don't endorse soluble antigens and are activated only when an antigen presenting cell expose them through the MHC (mayor histocompatibility complex) a processed antigen captured surrounded by the periphery and transported to the limph node, these APC in the periphery are called dendritic cells. It turns out that the B lymphocytes are also antigen presenting cell and once it recognizes the antigen they also process them and expose epitopes of the antigen to a previously activated T cell. For the cooperation between B and T cells to be succesful it's not necesary that both authorize the same epitope (since B's recognize epitopes present in soluble antigens and T cell recognize epitopes from the processed antigens) but they must recognize epitopes of the same antigen. When this occur, the T cell express chemical factors that induce the proliferation of the B cell. Some B cells (all clones producing the same BCR and antibodies) consequently differenciate into plasma cells able to produce large amounts of soluble M antibodies. Some B cell then, experience another complex process called "somatic hypermutation" which allows them to mature even more their affinity by their antigen and next change the type of antibody produced, then they differentiate into plasma cells but producing G isotype antibodies.
Some of these B cell resulting from somatic hypermutation don't differentiate to plasma cells instead they migrate through tissues and the bone marrow waiting for the antigens, these are called B memory cell.
By the way.., you said contained by one of your statements, "many antibody templates exist", this is not part of an adaptative immune response but the statement is true. There are B lymphocytes call B1 cells producing antibodies to antigens never exposed to. These are called natural antibodies specially adjectives for certain capsulated bacterias. Very young childs have this T independent imperviousness (B1 cells don't need antigens or T helper cell colaboration to produce antibodies) not totally developed and this is a reason why childs are more susceptible to infections by these patogens like Haemophilus influenza, Streptococcus pneumoniae etc specially until 2 years of age. Source(s): immunology classes
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