Developmental Regulation of B Lymphocyte Immune Tolerance Compartmentalizes Clonal Selection from Receptor Selection

AbstractB lymphocyte development is a highly ordered process that involves immunoglobulin gene rearrangements, antigen receptor expression, and a learning process that minimizes the development of cells with reactivity to self tissue. Two distinct mechanisms for immune tolerance have been defined that operate during early bone marrow stages of B cell development: apoptosis, which eliminates clones of cells, and receptor editing, which spares the cells but genetically reprograms their autoreactive antigen receptors through nested immunoglobulin L chain gene rearrangements. We show here that sensitivity to antigen-induced apoptosis arises relatively late in B cell development and is preceded by a functionally distinct developmental stage capable of receptor editing. This regulation compartmentalizes clonal selection from receptor selection

Percolation properties of the 2D Heisenberg model

We analyze the percolation properties of certain clusters defined on configurations of the 2--dimensional Heisenberg model. We find that, given any direction \vec{n} in O(3) space, the spins almost perpendicular to \vec{n} form a percolating cluster. This result gives indications of how the model can avoid a previously conjectured Kosterlitz-Thouless phase transition at finite temperature T.Comment: 4 pages, 3 eps figures. Revised version (more clear abstract, some new references

γδ T cells affect IL-4 production and B-cell tolerance

γδ T cells can influence specific antibody responses. Here, we report that mice deficient in individual γδ T-cell subsets have altered levels of serum antibodies, including all major subclasses, sometimes regardless of the presence of αβ T cells. One strain with a partial γδ deficiency that increases IgE antibodies also displayed increases in IL-4–producing T cells (both residual γδ T cells and αβ T cells) and in systemic IL-4 levels. Its B cells expressed IL-4–regulated inhibitory receptors (CD5, CD22, and CD32) at diminished levels, whereas IL-4–inducible IL-4 receptor α and MHCII were increased. They also showed signs of activation and spontaneously formed germinal centers. These mice displayed IgE-dependent features found in hyper-IgE syndrome and developed antichromatin, antinuclear, and anticytoplasmic autoantibodies. In contrast, mice deficient in all γδ T cells had nearly unchanged Ig levels and did not develop autoantibodies. Removing IL-4 abrogated the increases in IgE, antichromatin antibodies, and autoantibodies in the partially γδ-deficient mice. Our data suggest that γδ T cells, controlled by their own cross-talk, affect IL-4 production, B-cell activation, and B-cell tolerance

B-cell anergy: from transgenic models to naturally occurring anergic B cells?

Anergy, a condition in which cells persist in the periphery but are unresponsive to antigen, is responsible for silencing many self-reactive B cells. Loss of anergy is known to contribute to the development of autoimmune diseases, including systemic lupus erythematosus and type 1 diabetes. Multiple transgenic mouse models have enabled the dissection of mechanisms that underlie anergy, and recently, anergic B cells have been identified in the periphery of wild-type mice. Heterogeneity of mechanistic concepts developed using model systems has complicated our understanding of anergy and its biological features. In this Review, we compare and contrast the salient features of anergic B cells with a view to developing unifying mechanistic hypotheses that explain their lifestyles

Susceptibility and Percolation in 2D Random Field Ising Magnets

The ground state structure of the two-dimensional random field Ising magnet is studied using exact numerical calculations. First we show that the ferromagnetism, which exists for small system sizes, vanishes with a large excitation at a random field strength dependent length scale. This {\it break-up length scale} $L_b$ scales exponentially with the squared random field, $\exp(A/\Delta^2)$. By adding an external field $H$ we then study the susceptibility in the ground state. If $L>L_b$, domains melt continuously and the magnetization has a smooth behavior, independent of system size, and the susceptibility decays as $L^{-2}$. We define a random field strength dependent critical external field value $\pm H_c(\Delta)$, for the up and down spins to form a percolation type of spanning cluster. The percolation transition is in the standard short-range correlated percolation universality class. The mass of the spanning cluster increases with decreasing $\Delta$ and the critical external field approaches zero for vanishing random field strength, implying the critical field scaling (for Gaussian disorder) $H_c \sim (\Delta -\Delta_c)^\delta$, where $\Delta_c = 1.65 \pm 0.05$ and $\delta=2.05\pm 0.10$. Below $\Delta_c$ the systems should percolate even when H=0. This implies that even for H=0 above $L_b$ the domains can be fractal at low random fields, such that the largest domain spans the system at low random field strength values and its mass has the fractal dimension of standard percolation $D_f = 91/48$. The structure of the spanning clusters is studied by defining {\it red clusters}, in analogy to the ``red sites'' of ordinary site-percolation. The size of red clusters defines an extra length scale, independent of $L$.Comment: 17 pages, 28 figures, accepted for publication in Phys. Rev.

Finite temperature effects on cosmological baryon diffusion and inhomogeneous Big-Bang nucleosynthesis

We have studied finite temperature corrections to the baryon transport cross sections and diffusion coefficients. These corrections are based upon the recently computed renormalized electron mass and the modified state density due to the background thermal bath in the early universe. It is found that the optimum nucleosynthesis yields computed using our diffusion coefficients shift to longer distance scales by a factor of about 3. We also find that the minimum value of $^4 He$ abundance decreases by $\Delta Y_p \simeq 0.01$ while $D$ and $^7 Li$ increase. Effects of these results on constraints from primordial nucleosynthesis are discussed. In particular, we find that a large baryonic contribution to the closure density (\Omega_b h_{50}^{2} \lsim 0.4) may be allowed in inhomogeneous models corrected for finite temperature.Comment: 7 pages, 6 figures, submitted to Phys. Rev.