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Author(s): Aisha Siddiqa [1, 2]; Jennifer C. Sims-Mourtada [1, 2]; Liliana Guzman-Rojas [1, 2]; Roberto Rangel [1, 2]; Christiane Guret [3]; Vicente Madrid-Marina [4]; Yan Sun [2]; Hector Martinez-Valdez (corresponding [...]

Abstract Background Intrathymic development and selection of the T lymphocyte repertoire is restricted by the interactions of the T cell antigen receptor and CD4 or CD8 co-receptors with self major histocompatibility complex molecules. Positive or negative selection depends on a tight regulatory control of CD4 and CD8 expression. Determining the intracellular signals that differentially regulate the expression of CD4 and CD8 is important to understand the mechanisms that are implicated in selection of single positive CD4+CD8- or CD4-CD8+. Results The present study shows that stimulation of human thymocytes by phorbol esters or cAMP result in a differential regulation of CD4 and CD8 expression, both at the mRNA and cell surface glycoprotein level. Conclusions The differential regulation of CD4 and CD8 gene expression suggests that the selective activation of protein kinase C (PKC) and cAMP-dependent protein kinases (PKA) may be required for the selection of single positive CD4+CD8- and CD4-CD8+ cells during Intrathymic differentiation

Background: Intrathymic development and selection of the T lymphocyte repertoire is restricted by the interactions of the T cell antigen receptor and CD4 or CD8 co-receptors with self major histocompatibility complex molecules. Positive or negative selection depends on a tight regulatory control of CD4 and CD8 expression. Determining the intracellular signals that differentially regulate the expression of CD4 and CD8 is important to understand the mechanisms that are implicated in selection of single positive CD4+CD8- or CD4-CD8+. Results: The present study shows that stimulation of human thymocytes by phorbol esters or cAMP result in a differential regulation of CD4 and CD8 expression, both at the mRNA and cell surface glycoprotein level. Conclusions: The differential regulation of CD4 and CD8 gene expression suggests that the selective activation of protein kinase C (PKC) and cAMP-dependent protein kinases (PKA) may be required for the selection of single positive CD4+CD8- and CD4-CD8+ cells during Intrathymic differentiation [ABSTRACT FROM AUTHOR]

By confining germline transcription as a byproduct of the mechanisms inherent to genetic rearrangements, the translation of respective mRNAs and their biological relevance might have been overlooked. Here we report the identification, cloning, and biochemical characterization of a human Vκ-like protein that is encoded by a germline transcript. This surrogate protein assembles with the immunoglobulin μ heavy chain at the surface of B cell progenitors and precursors to form a κ-like antigen receptor. These findings support the notion that germline transcription is not futile and stress the flexibility in eukaryotic gene usage and expression. In addition, the present study confirms the co-existence of surrogate λ and κ receptors that are proposed to work in concert to promote B lymphocyte maturation. [ABSTRACT FROM AUTHOR]

After the demonstration that surrogate JCkappa polypeptides could covalently bind mu heavy chain and upon the characterization of the Vkappa-like component of the kappa-like pre-B cell receptor, it became evident that germline transcription is not sterile. The present review discusses the concept of the alternative usage of kappa-like pre-B cell receptors and classical pre-B cell receptors utilizing the lambda-like surrogate light chain composed of lambda5 and VpreB. We propose that both kappa-like and lambda-like pre-B cell receptors work in concert in a fail-safe mechanism to promote light chain rearrangement, heavy chain allelic exclusion and B-lymphocyte maturation.

By confining germline transcription as a byproduct of the mechanisms inherent to genetic rearrangements, the translation of respective mRNAs and their biological relevance might have been overlooked. Here we report the identification, cloning, and biochemical characterization of a human Vkappa-like protein that is encoded by a germline transcript. This surrogate protein assembles with the immunoglobulin mu heavy chain at the surface of B cell progenitors and precursors to form a kappa-like antigen receptor. These findings support the notion that germline transcription is not futile and stress the flexibility in eukaryotic gene usage and expression. In addition, the present study confirms the co-existence of surrogate lambda and kappa receptors that are proposed to work in concert to promote B lymphocyte maturation.