Analysis of the structural correlates for antibody polyreactivity by multiple reassortments of chimeric human immunoglobulin heavy and light chain V segments.

Polyreactive antibodies (Abs) constitute a major proportion of the early Ab repertoire and are an important component of the natural defense mechanisms against infections. They are primarily immunoglobulin M (IgM) and bind a variety of structurally dissimilar self and exogenous antigens (Ags) with moderate affinity. We analyzed the contribution of Ig polyvalency and of heavy (H) and light (L) chain variable (V) regions to polyreactivity in recombinatorial experiments involving the VH-diversity(D)-JH and V kappa-J kappa gene segments of a human polyreactive IgM, monoclonal antibody 55 (mAb55), and those of a human monoreactive anti-insulin IgG, mAb13, in an in vitro C gamma l and C kappa human expression system. These mAbs are virtually identical in their VH and V kappa gene segment sequences. First, we expressed the VH-D-JH and V kappa-J kappa genes of the IgM mAb55 as V segments of an IgG molecule. The bivalent recombinant IgG Ab bound multiple Ags with an efficiency only slightly lower than that of the original decavalent IgM mAb55, suggesting that class switch to IgG does not affect the Ig polyreactivity. Second, we coexpressed the mAb55-derived H or kappa chain with the mAb13-derived kappa or H chain, respectively. The hybrid IgG Ab bearing the mAb55-derived H chain V segment paired with the mAb13-derived kappa V segment, but not that bearing the mAb13-derived H chain V segment paired with the mAb55-derived kappa V segment, bound multiple Ags, suggesting that the Ig H chain plays a major role in the Ig polyreactivity. Third, we shuffled the framework 1 (FR1)-FR3 and complementarity determining region 3 (CDR3) regions of the H and kappa chain V segments of the mAB55-derived IgG molecule with the corresponding regions of the monoreactive IgG mAb13. The mAb55-derived IgG molecule lost polyreactivity when the H chain CDR3, but not the FR1-FR3 region, was replaced by the corresponding region of mAb13, suggesting that within the H chain, the CDR3 provides the major structural correlate for multiple Ag-binding. This was formally proved by the multiple Ag-binding of the originally monoreactive mAb13-derived IgG molecule grafted with the mAb55-derived H chain CDR3. The polyreactivity of this chimeric IgG was maximized by grafting of the mAb55-derived kappa chain FR1-FR3, but not that of the kappa chain CDR3.(ABSTRACT TRUNCATED AT 400 WORDS

Cataloguing PL 4-manifolds by gem-complexity

We describe an algorithm to subdivide automatically a given set of PL n-manifolds (via coloured triangulations or, equivalently, via crystallizations) into classes whose elements are PL-homeomorphic. The algorithm, implemented in the case n=4, succeeds to solve completely the PL-homeomorphism problem among the catalogue of all closed connected PL 4-manifolds up to gem-complexity 8 (i.e., which admit a coloured triangulation with at most 18 4-simplices). Possible interactions with the (not completely known) relationship among different classification in TOP and DIFF=PL categories are also investigated. As a first consequence of the above PL classification, the non-existence of exotic PL 4-manifolds up to gem-complexity 8 is proved. Further applications of the tool are described, related to possible PL-recognition of different triangulations of the K3-surface.Comment: 25 pages, 5 figures. Improvements suggested by the refere

Computing Matveev's complexity via crystallization theory: the boundary case

The notion of Gem-Matveev complexity has been introduced within crystallization theory, as a combinatorial method to estimate Matveev's complexity of closed 3-manifolds; it yielded upper bounds for interesting classes of such manifolds. In this paper we extend the definition to the case of non-empty boundary and prove that for each compact irreducible and boundary-irreducible 3-manifold it coincides with the modified Heegaard complexity introduced by Cattabriga, Mulazzani and Vesnin. Moreover, via Gem-Matveev complexity, we obtain an estimation of Matveev's complexity for all Seifert 3-manifolds with base $\mathbb D^2$ and two exceptional fibers and, therefore, for all torus knot complements.Comment: 27 pages, 14 figure

Viruses disrupt functions of human lymphocytes. Effects of measles virus and influenza virus on lymphocyte-mediated killing and antibody production.

We present experimental data that offer, in part, a better understanding of the immunosuppression that accompanies measles virus infection. We note that measles virus "silently" infects human lymphocytes and that the infection does not alter lymphocyte survival in vitro. Yet such infected lymphocytes fail to generate natural killer (NK) cell activity or synthesize immunoglobulins (Ig). Thus, the presence of virus within lymphocytes impairs their specific immune functions in the absence of cytolysis. Influenza virus also infects human lymphocytes. In contrast to measles virus infection of resting lymphocytes in which viral antigen is rarely expressed, influenza virus infection of these cells yields viral antigens expressed in the cytoplasm and on the cell surface. Influenza virus-infected lymphocytes have normal NK cell activity but fail to synthesize IgG or IgM

Monoreactive high affinity and polyreactive low affinity rheumatoid factors are produced by CD5+ B cells from patients with rheumatoid arthritis.

In patients with rheumatoid arthritis (RA), circulating CD5+ B lymphocytes, but not CD5- B lymphocytes, are increased in number and size, exist in an activated state, spontaneously proliferate, and secrete Ig that binds to the Fc fragment of IgG. By constructing continuous mAb-secreting cell lines from CD5+ B lymphocytes, the properties and dissociation constants (Kd) of these antibodies were determined. Two types of rheumatoid factors (RFs) with discrete reactivities were produced. The first type is polyreactive and binds with relatively low affinity (Kd, 10(-5) mol/liter) to the Fc fragment of IgG. These antibodies are similar to those produced by CD5+ B cells from healthy subjects. The second type of RF is monoreactive and binds with higher affinity (Kd, 10(-7) mol/liter) to the Fc fragment of IgG. These latter autoantibodies are produced by CD5+ B cells of RA patients, but not healthy subjects. Long-term longitudinal studies are needed to determine the role of these two types of RFs in the pathogenesis of RA

High Resolution Near-Infrared Spectra of Protostars

We present new high resolution (R = 21,000) near-infrared (2 microns) spectroscopic observations of a sample of Class I and flat-spectrum protostellar objects in the rho Ophiuchi dark cloud. None of the five Class I spectra show CO v = 0 -- 2 absorption features, consistent with high K-band continuum veilings, 4 <= r_k <= 20 and fast stellar rotation, assuming that the underlying protostellar photospheres are of late spectral type, as is suggested by the low luminosities of most of these objects. Two of the flat-spectrum protostellar objects also show no absorption features and are likely to be highly veiled. The remaining two flat-spectrum sources show weak, broad absorptions which are consistent with an origin in quickly rotating (v sin i ~ 50 km / s) late-type stellar photospheres which are also strongly veiled, r_k = 3 - 4. These observations provide further evidence that: 1)-Class I sources are highly veiled at near-infrared wavelengths, confirming previous findings of lower resolution spectroscopic studies; and 2)- flat-spectrum protostars rotate more rapidly than classical T Tauri stars (Class II sources), supporting findings from a recent high resolution spectroscopic study of other flat-spectrum sources in this cloud. In addition our observations are consistent with the high rotation rates derived for two of the Class I protostellar objects in our sample from observations of variable hard X-ray emission obtained with the ASCA satellite. These observations suggest that certain Class I sources can rotate even more rapidly than flat-spectrum protostars, near breakup velocity.Comment: 16 pages including 2 tables and 2 figures (AASTeX 5.x) to be published in The Astronomical Journal July 200

Computing Matveev's complexity via crystallization theory: the orientable case

By means of a slight modification of the notion of GM-complexity introduced in [Casali, M.R., Topol. Its Appl., 144: 201-209, 2004], the present paper performs a graph-theoretical approach to the computation of (Matveev's) complexity for closed orientable 3-manifolds. In particular, the existing crystallization catalogue C-28 available in [Lins, S., Knots and Everything 5, World Scientific, Singapore, 1995] is used to obtain upper bounds for the complexity of closed orientable 3-manifolds triangulated by at most 28 tetrahedra. The experimental results actually coincide with the exact values of complexity, for all but three elements. Moreover, in the case of at most 26 tetrahedra, the exact value of the complexity is shown to be always directly computable via crystallization theory