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CD45RO: a marker for BCR-mediated selection.

S M Jackson1, N Harp, D Patel

  • 1Molecular Immunogenetics Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.

Scandinavian Journal of Immunology
|July 20, 2007
PubMed
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This study reveals that CD45RO expression on centrocytes correlates with increased somatic mutations, suggesting its role in B-cell selection and development within germinal centers. This finding aids in understanding B-cell maturation and immune responses.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Germinal center (GC) B-cell survival is minimally influenced by IgH sequence alone.
  • End-stage effector B cells exhibit higher mutation frequencies than founder GC B cells.
  • Somatic hypermutation and selection are key processes in adaptive immunity.

Purpose of the Study:

  • To develop an assay enriching for GC B cells with increasing somatic mutations.
  • To investigate the role of CD45RO expression in B-cell selection and mutation frequency.
  • To explore the relationship between CD45RO, B-cell activation, and developmental stage.

Main Methods:

  • Subdividing CD19(+)IgD(-)CD38(+)CD77(+) centroblasts (CB) and CD19(+)IgD(-)CD38(+)CD77(-) centrocytes (CC) into CD45RO fractions (RO(-), RO(+/-), RO(+)).

Related Experiment Videos

  • Assessing IgV(H)4 mutation frequency and selection characteristics across RO fractions.
  • Analyzing clonally related sequences and cell surface marker expression (CD69, surface Ig).
  • Inducing CD45RO expression via B-cell receptor (BCR) crosslinking.

    • Main Results:

    • Mutation frequency in IgV(H)4 transcripts increased with CD45RO expression in centrocytes (CC), but not centroblasts (CB).
    • Centrocytes (CC) showed an increase in replacement mutations correlating with CD45RO expression.
    • RO-expressing CC and CB populations exhibited increased CD69 expression and were enriched for surface Ig(+) cells.
    • BCR crosslinking significantly increased surface CD45RO on tonsillar and GC B cells.

    Conclusions:

    • CD45RO expression is associated with increased somatic mutations and selection in centrocytes.
    • The CD45RO-associated increase in mutations may be linked to BCR-mediated selection or developmental transitions.
    • CD45RO serves as a potential indicator of positive selection and ongoing B-cell maturation within germinal centers.