Longitudinal analysis of B cell repertoire and antibody gene rearrangements during early HIV infection

Ig protein and mRNA expression was examined in a collection of 18 monoclonal EBV-transformed B cell lines derived from five patients with X-linked agammaglobulinemia (XLA). A diversity of H and L chain isotypes were synthesized by these lines: the majority (12 lines) expressed mu kappa chains, while mu lambda (two lines), gamma kappa (one), gamma lambda (one), delta lambda (one), and alpha kappa (one) isotype expression was also observed. For all the mu kappa-producing XLA B cell lines, the mu and kappa mRNA transcripts were of native size, and sequence analysis across the regions of VHDJH and V kappa J kappa gene joining showed that Ig gene rearrangements occurred in a typical manner. A variety of VHDJH and V kappa J kappa gene rearrangements were observed, not only within the set of mu kappa+ XLA B cells as a whole, but also among the cell lines derived from single patients. Southern blot analysis for genomic Ig H chain gene rearrangements was done to fully assess the extent of clonal heterogeneity among multiple mu kappa+ XLA B cell lines derived from two patients; all the B cell lines possessed distinct gene rearrangement patterns demonstrating their clonal unrelatedness. Our findings indicate that the B cell repertoire in individual XLA patients is clonally diverse and that it is unlikely that the defect in B cell differentiation in XLA is the result of inefficient or ineffective rearrangement of Ig H or L chain genes. Rather, this study provides support for the idea that the XLA defect relates to a more generalized cellular function, such as regulating the proliferation and/or clonal expansion of cells of the B lymphoid lineage.

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Review for "Templated Insertions at VD and DJ junctions Create Unique B‐Cell Receptors in the Healthy B‐Cell Repertoire"

10.1002/eji.202048828/v1/review2 ◽

2018 ◽

Keyword(s):

B Cell ◽

B Cell Receptors ◽

Cell Repertoire ◽

Cell Receptors ◽

B Cell Repertoire

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Selection of the expressed B cell repertoire by infusion of normal immunoglobulin G in a patient with autoimmune thyroiditis

European Journal of Immunology ◽

10.1002/eji.1830231133 ◽

1993 ◽

Vol 23 (11) ◽

pp. 2945-2950 ◽

Cited By ~ 40

Author(s):

Gilles Dietrich ◽

Francisco J. Varela ◽

Vincent Hurez ◽

Majida Bouanani ◽

Michel D. Kazatchkine

Keyword(s):

B Cell ◽

Immunoglobulin G ◽

Autoimmune Thyroiditis ◽

Cell Repertoire ◽

B Cell Repertoire ◽

Selection Of

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Monoclonal CD5+ and CD5- B-lymphocyte expansions are frequent in the peripheral blood of the elderly

Blood ◽

10.1182/blood-2003-09-3277 ◽

2004 ◽

Vol 103 (6) ◽

pp. 2337-2342 ◽

Cited By ~ 164

Author(s):

Paolo Ghia ◽

Giuseppina Prato ◽

Cristina Scielzo ◽

Stefania Stella ◽

Massimo Geuna ◽

...

Keyword(s):

B Cell ◽

Peripheral Blood ◽

B Lymphocyte ◽

The Elderly ◽

Lymphocytic Leukemia ◽

Pcr Analysis ◽

Cell Repertoire ◽

Healthy Elderly ◽

B Cell Repertoire ◽

Igh Genes

Abstract The responsiveness and diversity of peripheral B-cell repertoire decreases with age, possibly because of B-cell clonal expansions, as suggested by the incidence of serum monoclonal immunoglobulins and of monoclonal chronic lymphocytic leukemia (CLL)–like B lymphocytes in clinically silent adults. We phenotyped peripheral blood cells from 500 healthy subjects older than 65 years with no history or suspicion of malignancies and no evidence of lymphocytosis. In 19 cases (3.8%) a κ/λ ratio of more than 3:1 or less than 1:3 was found: 9 were CD5+, CD19+, CD23+, CD20low, CD79blow, sIglow (classic CLL-like phenotype); 3 were CD5+, CD19+, CD23+, CD20high, CD79blow, sIglow (atypical CLL-like), and 7 were CD5-, CD19+, CD20high, CD23-, CD79bbright, FMC7+, sIgbright (non–CLL-like). In 2 subjects, 2 phenotypically distinct unrelated clones were concomitantly evident. No cases were CD10+. Polymerase chain reaction (PCR) analysis demonstrated a monoclonal rearrangement of IgH genes in 15 of 19 cases. No bcl-1 or bcl-2 rearrangements were detected. Using a gating strategy based on CD20/CD5/CD79 expression, 13 additional CLL-like B-cell clones were identified (cumulative frequency of classic CLL-like: 5.5%). Thus, phenotypically heterogeneous monoclonal B-lymphocyte expansions are common among healthy elderly individuals and are not limited to classic CLL-like clones but may have the phenotypic features of different chronic lymphoproliferative disorders, involving also CD5- B cells.

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