V(D)J recombination

Examples of V(D)J recombination in the following topics:

• Antibody Genes and Diversity

  • The first stage is called somatic, or V(D)J, which stands for variable, diverse, and joining regions recombination.
  • V(D)J recombination takes place in the primary lymphoid tissue (bone marrow for B cells, and thymus for T cells) and nearly randomly combines variable, diverse, and joining gene segments.
  • The second stage of recombination occurs after the B cell is activated by an antigen.
  • Affinity maturation occurs after V(D)J recombination, and is dependent on help from helper T cells.
  • Outline the two stages which result in antibody diversity: somatic (V(D)J) and recombination stages

• Antibodies: Classes and Affinity Maturation

  • This combination is called V(D)J recombination, discussed below.
  • The process of generating antibodies with increased binding affinities is called affinity maturation; this occurs in mature B cells after V(D)J recombination and is dependent on help from helper T cells.
  • Initially, naïve B cells express only cell-surface IgM and IgD with identical antigen binding regions.
  • Class switching occurs in the heavy chain gene locus by a mechanism called class switch recombination (CSR).
  • Mechanism of class switch recombination that allows isotype switching in activated B cells.

• Gene rearrangement within genomes

  • In meiosis and mitosis, recombination occurs between similar molecules (homologs) of DNA.
  • Genetic recombination and recombinational DNA repair also occurs in bacteria and archaea.
  • Recombination can be artificially induced in laboratory (in vitro) settings, producing recombinant DNA for purposes including vaccine development.
  • V(D)J recombination in organisms with an adaptive immune system is a type of site-specific genetic recombination that helps immune cells rapidly diversify to recognize and adapt to new pathogen.
  • Recombination can occur between DNA sequences that contain no sequence homology.

• Clonal Selection and B-Cell Differentiation

  • B cells mature in the bone marrow where they undergo VDJ recombination to produce unique receptors which do not react to self antigens.
  • An antibody is composed of two identical light (L) and two identical heavy (H) chains, and the genes specifying them are found in the 'V' (Variable) region and the 'C' (Constant) region.
  • In the heavy-chain 'V' region there are three segments; V, D and J, which recombine randomly, in a process called VDJ recombination, to produce a unique variable domain in the immunoglobulin of each individual B cell.
  • Similar rearrangements occur for the light-chain 'V' region except there are only two segments involved; V and J.

• Maturation of B Cells

  • An antibody is composed of two identical light (L) and two identical heavy (H) chains, and the genes specifying them are found in the 'V' (Variable) region and the 'C' (Constant) region.
  • In the heavy-chain 'V' region there are three segments; V, D, and J, that recombine randomly, in a process called VDJ recombination, to produce a unique variable domain in the immunoglobulin of each individual B cell.
  • Similar rearrangements occur for light-chain 'V' region except there are only two segments involved; V and J.

• Bound-Free Transitions and Milne Relations

  • $\displaystyle dw = \frac{8\pi^2}{3 \hbar^2 c} | {\bf d}_{if} |^2 \left [ \frac{dn}{dp d\Omega} dp d\Omega \right ] J_\nu$
  • $\displaystyle \frac{dN}{dA dt} = 4\pi \frac{J_\nu}{\hbar \omega} d\nu = 4\pi \frac{J_\nu}{2\pi \hbar\omega} d\omega$
  • $\displaystyle \frac{d\sigma}{d\Omega} = \frac{p V m \omega}{6\pi c \hbar^3} |{\bf d}_{if} |^2 .$
  • Let $\sigma_{fb}(v)$ be the cross section for recombination for electrons with velocity $v$, then we have a recombination rate per unit volume of
  • where we have used $h\nu = \frac{1}{2} m v^2 + E_I$ to eliminate $d\nu$ and $dv$.

• Emission

  • Let's define the spontaneous emission coefficient, $j$.
  • $\epsilon_\nu$ is simply related to $j_\nu$ for an isotropic emitter
  • We know what $I_\nu$ is and we will spend much effort figuring out what $j_\nu$is for different physical systems.

• Antibody Structure

  • In B cells, the variable region of the light chain gene has 40 variable (V) and five joining (J) segments.
  • An enzyme called DNA recombinase randomly excises most of these segments out of the gene, splicing one V segment to one J segment.
  • During RNA processing, all but one V and J segment are spliced out.
  • Recombination and splicing may result in over 106 possible VJ combinations.
  • (a) As a germ-line B cell matures, an enzyme called DNA recombinase randomly excises V and J segments from the light chain gene.

• Particle Current

  • $\displaystyle J^\mu (x^\alpha) \equiv c \int \frac{d^3 {\bf p}}{E_{\bf p}} p^\mu f(x^\alpha, {\bf p}).$
  • $\displaystyle J^0(x^\alpha) = \int \frac{d^3 {\bf p}}{E_{\bf p}} c p^0 f(x^\alpha, {\bf p}) = \int d^3 {\bf p} f(x^\alpha, {\bf p}) = n(x^\alpha) \\ {\bf J}(x^\alpha) = \int \frac{d^3 {\bf p}}{E_{\bf p}} c {\bf p} f(x^\alpha, {\bf p}) = \frac{1}{c} \int d^3 {\bf p} {\bf v} f(x^\alpha, {\bf p}) = \frac{\langle {\bf v} \rangle}{c} n(x^\alpha) $
  • $\displaystyle J^{\mu}_{~~,\mu} = {J^\mu}{x^\mu} = n \langle \nabla_{\bf p} \cdot {\bf F} \rangle.$
  • Let's define ${\bf V}=\langle {\bf v} \rangle$ and write out the equation above by components,
  • $\displaystyle {n}{t} + \nabla \cdot \left (n {\bf V} \right ) = 0 $

• B.11 Chapter 11

  • $\displaystyle \frac{d (\rho v)}{d v} = \rho + v \frac{d \rho}{d v} = \rho \left ( 1 - \frac{v^2}{c_s^2} \right )$
  • $\displaystyle \frac{d j}{d v} = \rho \left [ 1 - \frac{v^2}{c_{s,0}^2} \left ( \frac{\rho}{\rho_0} \right )^{1-\gamma} \right ] = \frac{j}{v} \left [ 1 - \frac{v^2}{c_{s,0}^2} (\rho_0 v)^{\gamma-1} j^{1-\gamma} \right ]$
  • with $ j=\rho v$.
  • $\displaystyle j(v) = \rho_0 v \left [ 1 + \left ( 1 - \gamma \right ) \frac{v^2}{2 c_{s,0}^2} \right ]^{1/(\gamma-1)}$
  • $\displaystyle j_\mathrm{max} = \rho_0 c_{s,0} \left ( \frac{2^\gamma}{\gamma+1} \right )^{1/(\gamma-1)} \frac{1}{\sqrt{2\gamma+2}}$