Restoration of Ig Secretion: Mutation of Germline-Encoded Residues in T15L Chains Leads to Secretion of Free Light Chains and Assembled Antibody Complexes Bearing Secretion-Impaired Heavy Chains

Introduction. Immunoglobulins are molecules composed of two heavy and two light chains. Light chains are produced by B lymphocytes during the synthesis of immunoglobulins, and physiologically light chains are generally produced in excess compared to heavy chains. Light chains that are not combined to heavy chains in a whole immunoglobulin are called free light chains (FLCs). B-cell abnormalities are associated with disorders leading to an abnormal concentration of free light chains. In this study, we focus on the described changes of serum and cerebrospinal fluid concentration of free light chains in inflammatory disorders: multiple sclerosis, HIV infection, and HIV-associated lymphomas. Methods. We performed broad research of the literature pertaining to our investigation via the MEDLINE/PubMed database. Results. It has been proven that FLC determination can provide rapid information about intrathecal inflammation in patients with multiple sclerosis. Moreover, literature data suggest that free light chain determination is the most interesting alternative for oligoclonal band analysis. In the present review, we also described that HIV-related immune system dysfunction is associated with an elevated concentration of serum-free light chains. Additionally, FLCs are potentially a strong and sensitive predictor of the risk of developing HIV-associated lymphomas. Conclusion. Based on these published findings, we suggest that free light chains have high diagnostic sensitivity, which probably enables application in laboratory diagnostics.

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Free light chains and heavy/light chains pairs assay in diagnostics of multiple myeloma and other diseases related to plasmatic cells dyscrasias

Diagnostyka Laboratoryjna ◽

10.5604/01.3001.0013.7962 ◽

2017 ◽

Vol 53 (1) ◽

pp. 41-46

Author(s):

Ewelina Kudyba ◽

Tomasz Wróbel

Keyword(s):

Multiple Myeloma ◽

Residual Disease ◽

Protein Electrophoresis ◽

Light Chains ◽

Free Light Chains ◽

Heavy Chains ◽

Plasma Cell Neoplasms ◽

Single Clone ◽

Minimal Residual

Plasma cell neoplasms constitute a large group of diseases characterized by uncontrolled proliferation of a single clone of plasmocytes and production of monoclonal protein which may be present in patient’s serum in the form of intact immunoglobulins, free light immunoglobulin chains, or both of these molecules simultaneously. In addition to the methods commonly used for years for the determination of the protein such as protein electrophoresis or immunofixation, clinical standards in the last decade included the test for determining the concentration of κ and λ free light chains in serum. The test profile mentioned above has been complemented by a new method for identifying and determining the concentration of immunoglobulins with the possibility of recognizing the binding between pairs of heavy chains γ, α, μ and κ or λ light chains of immunoglobulins. It gives the opportunity to differentiate separately Ig’κ and Ig’λ molecules in each immunoglobulin class. Quantification of these sensitive and specific markers is used for the early diagnosis of the disease and it also provides the ability to accurately monitor the treatment, evaluate minimal residual disease and detect early the recurrence of monoclonal gammopathy like multiple myeloma.

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Structure of Myosin Subfragment-1 from Electron Microscopy and Crystallography

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100102869 ◽

1988 ◽

Vol 46 ◽

pp. 156-157

Author(s):

Donald A. Winkelmann

Keyword(s):

Electron Microscopy ◽

Molecular Weight ◽

Actin Filaments ◽

Light Chains ◽

Myosin Filament ◽

Primary Role ◽

Heavy Chains ◽

Myosin Subfragment ◽

Myosin Subfragment 1 ◽

Globular Head

The primary role of the interaction of actin and myosin is the generation of force and motion as a direct consequence of the cyclic interaction of myosin crossbridges with actin filaments. Myosin is composed of six polypeptides: two heavy chains of molecular weight 220,000 daltons and two pairs of light chains of molecular weight 17,000-23,000. The C-terminal portions of the myosin heavy chains associate to form an α-helical coiled-coil rod which is responsible for myosin filament formation. The N-terminal portion of each heavy chain associates with two different light chains to form a globular head that binds actin and hydrolyses ATP. Myosin can be fragmented by limited proteolysis into several structural and functional domains. It has recently been demonstrated using an in vitro movement assay that the globular head domain, subfragment-1, is sufficient to cause sliding movement of actin filaments.The discovery of conditions for crystallization of the myosin subfragment-1 (S1) has led to a systematic analysis of S1 structure by x-ray crystallography and electron microscopy. Image analysis of electron micrographs of thin sections of small S1 crystals has been used to determine the structure of S1 in the crystal lattice.

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